Abemaciclib 阿贝西利 Verzenios 唯择 礼来 2017/9/28 FDA/NMPA VERZENIO is a kinase inhibitor indicated: 1.in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence. 2 in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.3.in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.4.as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. 阿贝西利是一种激酶抑制剂，FDA批准其适应症包括：1.联合内分泌治疗（他莫昔芬/芳香化酶抑制剂）用于性激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性,淋巴结阳性，高复发风险的早期乳腺癌成年患者的辅助治疗。2.联芳香化酶抑制剂用于治疗激素受体(HR)阳性、人表皮生长因子受体2 (HER2)阴性的晚期或转移性乳腺癌的初期内分泌治疗。3.联合与氟维司群用于激素受体( HR )阳性、人类表皮生长因子受体2 ( HER2 )阴性的晚期或转移性乳腺癌的初始内分泌治疗后疾病进展的治疗。4.单药用于治疗既往接受内分泌治疗后疾病进展的HR阳性、HER2阴性的晚期或转移性乳腺癌成人患者。2020年NMPA批准阿贝西利适用于乳腺癌患者的治疗。 乳腺癌 Abemaciclib is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). These kinases are activated upon binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation. In vitro, continuous exposure to abemaciclib inhibited Rb phosphorylation and blocked progression from G1 into S phase of the cell cycle, resulting in senescence and apoptosis. In breast cancer xenograft models, abemaciclib dosed daily without interruption as a single agent or in combination with antiestrogens resulted in reduction of tumor size. BARD1是一种接头蛋白，当与BRCA1结合时具有E3连接酶活性（PMID: 11573085）。BRCA1是一个特征明确的肿瘤抑制因子，其功能是通过同源重组和细胞周期检查点激活来修复DNA双链断裂，从而维持基因组完整性（PMID: 11278247）。BARD1-BRCA1复合物涉及多种细胞进程，包括DNA修复、基因表达、复制叉稳定性维持以及染色质调节的各个阶段（PMID: 27239795）。BARD1与BRCA1相互作用，结合至新复制DNA上的损伤部位，并对组蛋白H2A的赖氨酸残基进行单泛素化修饰（PMID: 30804502）。然后，BARD1-BRCA1复合体介导DNA损伤部位的切除，将拮抗性修复蛋白53BP1驱逐出去，并募集一些DNA损伤反应蛋白（包括RAD51）到受损部位（PMID: 27239795）。聚（ADP-核糖）介导了早期BRCA1-BARD1复合物募集到受损DNA位点的过程（PMID: 25634209）。乳腺癌小鼠模型中BARD1的失活导致了与BRCA1缺失相似的表型，说明BRAD1和BRCA1可能有相似的基因功能（PMID: 18443292）。 FDA-approval:4/2023;NMPA-approval:12/2020 2023/6/2 sxz D0001
Ado-Trastuzumab Emtansine 恩美曲妥珠单抗 Kadcyla 赫赛莱 罗氏 2013-02-22 00:00:00 FDA/NMPA KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugate indicated, as a single agent, for 1.the treatment of patients with HER2-positive, metastatic breast cancer who previously （1)received trastuzumab and a taxane, separately or in combination. Patients should have either: received prior therapy for metastatic disease, or (2).developed disease recurrence during or within six months of completing adjuvant therapy. 2.the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. KADCYLA是一种HER2靶向抗体和微管抑制剂缀合物，FDA批准其适应症为：单药使用：1.以下既往接受过单独或联合曲妥珠单抗和紫杉烷治疗的HER2阳性转移性乳腺癌患者：(1)既往接受过转移性疾病的先前治疗。(2)完成辅助治疗期间或之后六个月内疾病复发。2.既往接受紫杉烷和曲妥珠单抗治疗后仍残留浸润性疾病的HER2阳性早期乳腺癌患者的辅助治疗。2020年NMPA批准其适应症为：早期乳腺癌：赫赛莱单药适用于接受了紫杉烷类联合曲妥珠单抗为基础的新辅助治疗后仍残存侵袭性病灶的 HER2 阳性早期乳腺癌患者的辅助治疗。2021年NMPA批准其适用于晚期乳腺癌：赫赛莱单药适用于接受了紫杉烷类和曲妥珠单抗治疗的 HER2 阳性、不可切除局部晚期或转移性乳腺癌患者（患者应具备以下任一情形既往接受过针对局部晚期或转移性乳腺癌的治疗，或在辅助治疗期间或完成辅助治疗后 6 个月内出现疾病复发）。 乳腺癌 Ado-trastuzumab emtansine is a HER2-targeted antibody-drug conjugate. The antibody is the humanized anti-HER2 IgG1, trastuzumab. The small molecule cytotoxin, DM1, is a microtubule inhibitor. Upon binding to sub-domain IV of the HER2 receptor, ado-trastuzumab emtansine undergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting in intracellular release of DM1-containing cytotoxic catabolites. Binding of DM1 to tubulin disrupts microtubule networks in the cell, which results in cell cycle arrest and apoptotic cell death. In addition, in vitro studies have shown that similar to trastuzumab, ado-trastuzumab emtansine inhibits HER2 receptor signaling, mediates antibody-dependent cell-mediated cytotoxicity and inhibits shedding of the HER2 extracellular domain in human breast cancer cells that overexpress HER2. 恩美曲妥珠单抗（Ado-trastuzumab emtansine）是靶向HER2的抗体药物偶联物。 该抗体是人源化抗HER2 IgG1曲妥珠单抗（Trastuzumab）。 小分子细胞毒素DM1是微管抑制剂。 与HER2受体的亚结构域IV结合后，恩美曲妥珠单抗（Ado-trastuzumab emtansine）经历受体介导的内在化和随后的溶酶体降解，从而导致胞内释放含DM1的细胞毒性代谢产物。 DM1与微管蛋白的结合会破坏细胞中的微管网络，从而导致细胞周期停滞和细胞凋亡。 此外，体外研究表明，与曲妥珠单抗（Trastuzumab）类似，恩美曲妥珠单抗（Ado-trastuzumab emtansine）抑制HER2受体信号传导，介导抗体依赖性细胞介导的细胞毒性，并抑制过表达HER2的人乳腺癌细胞中HER2的胞外域脱落。 FDA-approval: 4/2023;NMPA-approval:1/2020;NMPA-approval:1/2021 230728 pj D0003 修改中文商品名 LXL
Afatinib 阿法替尼 Gilotrif 吉泰瑞 勃林格殷格翰 2013/7/12 FDA/NMPA GILOTRIF is a kinase inhibitor indicated for: 1.First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test. 2.Treatment of patients with metastatic, squamous NSCLC progressing after platinum-based chemotherapy GILOTRIF是一种激酶抑制剂，FDA批准其适应症包括：1.携带非耐药性表皮生长因子受体(EGFR)突变的转移性非小细胞肺癌(NSCLC)的一线治疗。2.铂基化疗后疾病进展的转移性鳞状非小细胞肺癌。2017年NMPA批准其适用于非小细胞肺癌(NSCLC)患者的治疗。 非小细胞肺癌 Afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling.Certain mutations in EGFR, including non-resistant mutations in its kinase domain, can result in increased autophosphorylation of the receptor, leading to receptor activation, sometimes in the absence of ligand binding,and can support cell proliferation in NSCLC. Non-resistant mutations are defined as those occurring in exons constituting the kinase domain of EGFR that lead to increased receptor activation and where efficacy is predicted by 1) clinically meaningful tumor shrinkage with the recommended dose of afatinib and/or 2) inhibition of cellular proliferation or EGFR tyrosine kinase phosphorylation at concentrations of afatinib sustainable at the recommended dosage according to validated methods. The most commonly found of these mutations are exon 21 L858R substitutions and exon 19 deletions.Afatinib demonstrated inhibition of autophosphorylation and/or in vitro proliferation of cell lines expressing wild-type EGFR and in those expressing selected EGFR exon 19 deletion mutations, exon 21 L858R mutations, or other less common non-resistant mutations, at afatinib concentrations achieved in patients. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2.Treatment with afatinib resulted in inhibition of tumor growth in nude mice implanted with tumors either overexpressing wild type EGFR or HER2 or in an EGFR L858R/T790M double mutant model. 阿法替尼（Afatinib）与EGFR（ErbB1），HER2（ErbB2）和HER4（ErbB4）的激酶结构域共价结合，并不可逆地抑制酪氨酸激酶的自磷酸化，从而导致ErbB信号下调。EGFR的某些突变，包括其激酶结构域的非耐药性突变，可使受体自磷酸化增加，导致受体有时可在无配体结合的情况下激活，并促进NSCLC中的细胞增殖。非耐药性突变定义为发生在编码EGFR激酶结构域的外显子中并能导致受体激活增强的突变，其功效可通过以下方式预测：1）阿法替尼（Afatinib）推荐剂量治疗下有临床意义的肿瘤缩小，和/或2）根据验证方案，推荐剂量下可持续的阿法替尼（Afatinib）浓度下对细胞增殖或EGFR酪氨酸激酶磷酸化的抑制作用。这些突变中最常见的是外显子21 L858R替换和外显子19缺失。在以等价于患者服用剂量的阿法替尼（Afatinib）浓度培养的野生型EGFR细胞系和表达特定的EGFR外显子19缺失突变、外显子21 L858R突变或其他较罕见非耐药性突变的细胞系中，证实了阿法替尼（Afatinib）对自磷酸化和/或体外细胞增殖的抑制作用。此外，阿法替尼（Afatinib）也会抑制过表达HER2细胞系的体外增殖。在裸鼠移植瘤模型中过表达野生型EGFR或HER2，或者EGFRL858R/T790M双突变，经阿法替尼（Afatinib）治疗后均可抑制肿瘤的生长。 FDA-approval:10/2019;NMPA-approval:2017 2023/6/2 sxz D0004
Alectinib 阿来替尼 Alecensa 安圣莎 Excella GmbH 2015/12/11 FDA/NMPA ALECENSA is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. ALECENSA是一种激酶抑制剂，FDA批准其适用于间变性淋巴瘤激酶(ALK)阳性的转移性非小细胞肺癌(NSCLC)。2018年NMPA批准其单药适用于间变性淋巴瘤激酶（ALK）阳性的局部晚期或转移性非小细胞肺癌患者的治疗。 非小细胞肺癌 Alectinib is a tyrosine kinase inhibitor that targets ALK and RET. In nonclinical studies, alectinib inhibited ALK phosphorylation and ALK-mediated activation of the downstream signaling proteins STAT3 and AKT, and decreased tumor cell viability in multiple cell lines harboring ALK fusions, amplifications, or activating mutations. The major active metabolite of alectinib, M4, showed similar in vitro potency and activity.Alectinib and M4 demonstrated in vitro and in vivo activity against multiple mutant forms of the ALK enzyme, including some mutations identified in NSCLC tumors in patients who have progressed on crizotinib.In mouse models implanted with tumors carrying ALK fusions, administration of alectinib resulted in antitumor activity and prolonged survival, including in mouse models implanted intracranially with ALK-driven tumor cell lines. 阿来替尼(Alectinib)是靶向ALK和RET的酪氨酸激酶抑制剂。在非临床研究中，阿来替尼(Alectinib)抑制ALK磷酸化和ALK介导的下游信号蛋白STAT3和AKT的活化，并降低ALK融合、扩增或突变的多种细胞系中肿瘤细胞的活力。阿来替尼(Alectinib)的主要活性代谢产物M4，在体外也表现出相似的效价和活性。阿来替尼(Alectinib)和M4在体内和体外均对ALK酶的多种突变形式具有活性，包括在克唑替尼(Crizotinib)治疗的非小细胞肺癌肿瘤患者中鉴定出的某些突变。在携带ALK融合蛋白的肿瘤的小鼠模型中（包括在颅内植入ALK驱动的肿瘤细胞系的小鼠模型），使用阿来替尼(Alectinib)可产生抗肿瘤活性并延长生存期。 FDA-approval:10/2019;NMPA-approval:09/2021;NMPA-approval:2018 2023/6/20 sxz D0005 修改日期；sxz
Alpelisib 阿培利司 Piqray 诺华制药 2019/5/25 FDA PIQRAY is a kinase inhibitor indicated in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)- positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen. PIQRAY是一种激酶抑制剂，适用于联合氟维司群用于治疗既往接受内分泌治疗后疾病进展、携带PIK3CA突变、激素受体(HR)阳性、人表皮生长因子受体2 (HER2)阴性的绝经后妇女和男性晚期或转移性乳腺癌。 乳腺癌 Alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models.In breast cancer cell lines, alpelisib inhibited the phosphorylation of PI3K downstream targets, including Akt and showed activity in cell lines harboring a PIK3CA mutation. In vivo, alpelisib inhibited the PI3K/Akt signaling pathway and reduced tumor growth in xenograft models, including models of breast cancer.PI3K inhibition by alpelisib treatment has been shown to induce an increase in estrogen receptor (ER) transcription in breast cancer cells. The combination of alpelisib and fulvestrant demonstrated increased anti- tumor activity compared to either treatment alone in xenograft models derived from ER-positive, PIK3CA mutated breast cancer cell lines. 阿培利司（Alpelisib）是PI3Kα的抑制剂，主要具有针对PI3Kα的抑制活性。在体外和体内模型中，PIK3CA基因的获得性突变将导致PI3Kα和Akt信号通路的激活，从而使细胞性状发生转化以及促使肿瘤的产生。在乳腺癌细胞系中，阿培利司（Alpelisib）抑制PI3K下游靶标（包括Akt）的磷酸化，并在具有PIK3CA突变的细胞系中显示出活性。在体内，阿培利司（Alpelisib）在移植瘤模型（包括乳腺癌模型）中抑制PI3K/Akt信号通路并降低肿瘤生长。通过阿培利司（Alpelisib）治疗抑制PI3K已显示出可诱导乳腺癌细胞中雌激素受体（ER）转录的增加。在ER阳性、PIK3CA突变的乳腺癌细胞系的移植瘤模型中，阿培利司（Alpelisib）和氟维司琼（Fulvestrant）联合治疗显示出较单一治疗更强的抗肿瘤活性。 07/2021 2021/11/26 D0007
Amivantamab-vmjw 埃万妥单抗 Rybrevant 杨森生物 2021/5/21 0:00 FDA RYBREVANT is a bispecific EGF receptor-directed and MET receptor directed antibody indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. RYBREVANT是一种EGFR/MET双特异性抗体，适用于铂类化疗期间或之后疾病进展的携带表皮生长因子受体(EGFR)20号外显子插入突变的局部晚期或转移性非小细胞肺癌(NSCLC)成人患者。 非小细胞肺癌 Amivantamab-vmjw is a bispecific antibody that binds to the extracellular domains of EGFR and MET.In in vitro and in vivo studies amivantamab-vmjw was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 20 insertion mutation models, degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity (ADCC) and trogocytosismechanisms, respectively. Amivantamab-vmjw是一种双特异性抗体，可与EGFR和MET的胞外域结合。在体外和体内研究中，amivantamab-vmjw能够通过阻断配体结合，且在EGFR 20号外显子插入突变模型中导致EGFR和MET降解，进而抑制EGFR和MET信号传导功能。此外，肿瘤细胞表面存在的EGFR和MET还可以分别通过抗体依赖性细胞毒性(ADCC)和吞噬作用机制，将这些细胞靶向以被免疫效应细胞（例如自然杀伤细胞和巨噬细胞）破坏。 05/2021 231103 pj D0009 新增药物中文名称 SXZ
Asciminib Scemblix 诺华制药 2021/10/29 FDA SCEMBLIX is a kinase inhibitor indicated for the treatment of adult patients with:1.Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). 2.Ph+ CML in CP with the T315I mutation. SCEMBLIX是一种激酶抑制剂，用于治疗患有以下疾病的成年患者：其适应症包括：1.既往接受过两种或两种以上酪氨酸激酶抑制剂（TKI）治疗的慢性期（CP）费城染色体阳性慢性髓系白血病（Ph+CML）。2.携带T315I突变的慢性期Ph+CML。 慢性髓系白血病 Asciminib is an ABL/BCR-ABL1 tyrosine kinase inhibitor. Asciminib inhibits the ABL1 kinase activity of the BCRABL1 fusion protein, by binding to the ABL myristoyl pocket. In studies conducted in vitro or in animal models of CML, asciminib showed activity against wild-type BCR-ABL1 and several mutant forms of the kinase, including the T315I mutation. Asciminib是一种ABL/BCR-ABL1酪氨酸激酶抑制剂。Asciminib通过与ABL肉豆蔻酰口袋结合，抑制BCRABL1融合蛋白的ABL1激酶活性。在体外试验或CML动物模型研究中，Asciminib显示出对野生型BCR-ABL1和激酶的几种突变（包括T315I突变）的活性。 10/2021 Asciminib (ABL001)是一种有效的、选择性的ABL1变构抑制剂，Kd值为0.5-0.8nM，与ABL1的十四酰口袋结合。ABL001是一种有效的、选择性的BCR-ABL抑制剂，对多数突变型都具有活性，如T315I。ABL001与ABL1的调节位点的结合，在野生型ABL中，这一位点通常是被一个肉豆蔻酰基团所占据。ABL001通过不同于其他靶向催化位点的抑制剂机理抑制了ABL激酶活性。它与BCR-ABL激酶区域的口袋结合，正常状态下，这一区域为ABL1的十八烷基化N端所占，一旦与BCR结合，作用于ABL1自我调节功能的十八烷基化N端丢失。ABL001通过结合这一空白位点，模拟了十八烷基化N端的作用，从而恢复了激酶活性的负向调控功能。浓度为1-10 nM的ABL001可选择性地抑制CML和Ph+ ALL细胞的生长；而即使在浓度高达1000倍以上时，BCR-ABL-阴性细胞不受ABL001的影响。ABL001与ABL的肉豆蔻酰口袋结合的离解常数Kd为0.5-0.8 nM，诱导失活的C端螺旋构象。ABL001对所检测的60多种激酶没有活性，其中包括SRC；同时对G蛋白偶联受体、离子通道、核受体和转运体也没有活性。因此ABL001具有高选择性。在KCL-22小鼠移植瘤模型中，ABL001具有有效的抗肿瘤活性，能够引起完全的肿瘤消退，并与pSTAT5抑制效果呈浓度依赖性关系。ABL001具有中等的口服吸收度、体内体积分布和半衰期。它作为单药进行给药时，能够诱导临床的抗肿瘤活性，在既往多次化疗的CML（慢性髓细胞性白血病）患者中耐受良好。至于其药代动力学、药效学，在小鼠、大鼠和狗中单次静脉注射1mg/kg, 2mg/kg和1mg/kg的ABL001，血浆清除率（CL）分别为12, 16和6 mL/min/kg。在小鼠和狗中，单次静脉注射1 mg/kg ABL001，T1/2term分别为1.1和3.7小时。在大鼠中，单次静脉注射2 mg/kg，T1/2term为2.7小时。对小鼠和大鼠口服以30 mg/kg ABL001后，其口服生物利用度分别为35%和27%；而在狗中，口服以15 mg/kg ABL001，口服生物利用度为111%。 2021/11/26 pj/sjz D0012
ASP3026 ASP3026 has been used in trials studying the treatment of Solid Tumor, B-Cell Lymphoma, Advanced Malignancies, Positive for Anaplastic Lymphoma Kinase, and Positive for Proto-Oncogene Tyrosine-Protein Kinase ROS. ASP3026已用于实体瘤、B细胞淋巴瘤、晚期恶性肿瘤、间变性淋巴瘤激酶阳性和原癌基因酪氨酸蛋白激酶ROS阳性治疗的临床试验。 2021/11/26 D0013
Atezolizumab 阿替利珠单抗 Tecentriq 泰圣奇 基因泰克 2016/5/18 FDA/NMPA TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: 1.Urothelial Carcinoma ：for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who:are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 5% of the tumor area), as determined by an FDA-approved test, or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 2. Non-Small Cell Lung Cancer (NSCLC): (1)as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test. (2)for the first-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 stained ≥ 50% of tumor cells [TC ≥ 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 10% of the tumor area [IC ≥ 10%] ), as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. (3)in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. (4)in combination with paclitaxel protein-bound and carboplatin for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. (5)for the treatment of adult patients with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving TECENTRIQ 3.Small Cell Lung Cancer：in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). 4.Hepatocellular Carcinoma :in combination with bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy.5.Melanoma:in combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. TECENTRIQ是一种程序性死亡配体1(PD-L1)阻断抗体，其适应症包括：1.下列局部晚期或转移性尿路上皮癌成人患者：(1)不适用顺铂化疗、且肿瘤表达PD-L1(PD-L1染色的肿瘤浸润免疫细胞[IC]覆盖≥5%肿瘤面积)。(2)不论PD-L1的状态如何，均不适用任何含铂化疗。2.转移性非小细胞肺癌(NSCLC)：(1) 用于（肿瘤细胞中PD-L1表达≥1%）II - IIIA期非小细胞肺癌切除和铂基化疗后的辅助治疗。(2)用于肿瘤高表达PD-L1(PD-L1染色≥50%肿瘤细胞[TC≥50%]或PD-L1染色的肿瘤浸润免疫细胞[IC]覆盖≥10%的肿瘤面积[IC≥10%])、无EGFR或ALK基因组肿瘤异常的转移性NSCLC成人患者的一线治疗。(3)联合贝伐珠单抗、紫杉醇和卡铂用于无EGFR或ALK基因组肿瘤异常的转移性非鳞状NSCLC成人患者的一线治疗。(4)联合蛋白结合型紫杉醇和卡铂用于无EGFR或ALK基因组肿瘤异常的转移性非鳞状NSCLC成人患者的一线治疗。（5）用于治疗接受含铂化疗期间或之后疾病进展的转移性NSCLC成人患者。3. 小细胞肺癌：联合卡铂和依托泊苷用于广泛期小细胞肺癌(ES-SCLC)成人患者的一线治疗。4. 肝细胞癌：联合贝伐珠单抗用于治疗既往未接受系统性治疗的不可切除性或转移性肝细胞癌(HCC)患者。5.黑色素瘤：联合考比替尼和维莫非尼用于治疗BRAF V600突变
Avapritinib 阿伐替尼 Ayvakit 泰吉华 蓝图医药 2020/1/9 FDA/NMPA AYVAKIT is a kinase inhibitor indicated for: 1. Gastrointestinal Stromal Tumor (GIST): the treatment of adults with unresectable or metastatic GIST harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. 2.Advanced Systemic Mastocytosis (AdvSM):(1)the treatment of adult patients with AdvSM. AdvSM includes patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). AYVAKIT是一种激酶抑制剂，其适应症为：1.携带血小板来源生长因子受体α (PDGFRA)基因18号外显子突变(包括PDGFRA D842V突变)的不可切除性或转移性胃肠道间质瘤(GIST)成人患者。2.晚期系统性肥大细胞增多症：用于治疗晚期系统性肥大细胞增多成人患者，包括侵袭性全身性肥大细胞增多症(ASM)、伴相关血液学肿瘤的全身性肥大细胞增多(SMAHN)和肥大细胞白血病(MCL)患者。2021年NMPA批准其适用于胃肠道间质瘤（GIST)成人患者。 胃肠道间质瘤、肥大细胞增多症 Avapritinib is a tyrosine kinase inhibitor that targets PDGFRA and PDGFRA D842 mutants as well as multiple KIT exon 11, 11/17 and 17 mutants with half maximal inhibitory concentrations (IC50s) less than 25 nM. Certain mutations in PDGFRA and KIT can result in the autophosphorylation and constitutive activation of these receptors which can contribute to tumor cell proliferation. Other potential targets for avapritinib include wild type KIT, PDGFRB, and CSFR1.In in vitro cellular assays, avapritinib inhibited the autophosphorylation of KIT D816V and PDGFRA D842V, mutants associated with resistance to approved kinase inhibitors, with IC50 of 4 nM and 30 nM, respectively. Avapritinib also had anti-tumor activity in mice implanted with an imatinib-resistant patient- derived xenograft model of human GIST with activating KIT exon 11/17 mutations. 阿伐替尼(Avapritinib)是一种酪氨酸激酶抑制剂，靶向PDGFRA和PDGFRA D842突变体以及多个KIT外显子11、11/17和17突变体，其最大半数抑制浓度（IC50s）小于25nM。PDGFRA和KIT中的某些突变会导致这些受体的自磷酸化和组成性激活，从而导致肿瘤细胞增殖。阿伐替尼(Avapritinib)的其他潜在靶标包括野生型KIT，PDGFRB和CSFR1。在体外细胞试验中，阿伐替尼(Avapritinib)可抑制KIT D816V和PDGFRA D842V的自磷酸化（IC50分别为4nM和30nM条件），这些突变会对已批准的激酶抑制剂产生耐药。在移植有激活的KIT外显子11/17突变的伊马替尼（Imatinib）耐药人源GIST移植瘤小鼠模型中，阿伐替尼(Avapritinib)也具有抗肿瘤活性。 FDA-approval:06/2021;NMPA-approval:2021 2023/6/20 sxz D0015
AZD8186 AZD-8186 is under investigation in clinical trial NCT03218826 (PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery). AZD-8186正在开展临床试验NCT03218826（PI3Kβ抑制剂AZD8186和多西他赛[Docetaxel]用于治疗转移性或无法通过手术切除的PTEN或PIK3CB突变的晚期实体瘤患者）。 2021/11/26 D0018
AZD9496 AZD-9496 is under investigation in clinical trial NCT02248090 (AZD9496 First Time in Patients Ascending Dose Study). AZD9496 是有效,选择性的雌激素受体 (ERα) 拮抗剂，IC50 为 0.28 nM。AZD9496 是一种口服有效的选择性雌激素受体降解剂 (SERD)。 AZD-9496正在开展临床试验NCT02248090（AZD9496首次在患者中的剂量递增研究）。 231008 pj D0019 新增作用机制内容 LXL
Refametinib RDEA119 is a potent, non-ATP competitive, highly selective inhibitor of MEK. RDEA119 is a highly potent and selective inhibitor of mitogen-activated ERK kinase (MEK), a key component of the RAS/RAF/MEK/ERK pathway that is commonly defective in human tumors. The MEK1/2 pathway is important in cell cycle regulation in inflammatory bowel disease, including ulcerative colitis and Crohn's disease. RDEA119 was shown to reduce damage to colonic tissue in two different mouse models of colitis, murine trinitrobenzene sulfonic acid (TNBS) colitis model and murine dextran sulfate sodium (DSS) colitis model. [Ardea Biosciences Inc. Press release] Refametinib (BAY 869766; RDEA119) 是一种口服有效，非ATP竞争的，选择性 MEK1/MEK2 变构抑制剂，IC50 分别为 19 nM 和 47 nM。 RDEA119是一种有效的，非ATP竞争性的，高选择性的MEK抑制剂。RDEA119是有丝分裂原激活的ERK激酶（MEK）的高效选择性抑制剂，ERK激酶是RAS/RAF/MEK/ERK途径的关键成分，通常在人类肿瘤中具有缺陷。MEK1/2途径在炎症性肠病（包括溃疡性结肠炎和克罗恩病）的细胞周期调控中发挥重要作用。在两种不同的三硝基苯磺酸（TNBS）和葡聚糖硫酸盐钠（DSS）诱导的小鼠结肠炎模型中，RDEA119可减少对结肠组织的损害。 [Ardea Biosciences Inc.新闻稿] 231007 pj D0020 新增作用机制内容，删除中文名称 LXL
Bevacizumab 贝伐珠单抗 Avastin 安维汀 基因泰克 2004/2/26 FDA/NMPA Avastin is a vascular endothelial growth factor inhibitor indicated for the treatment of:1.Metastatic colorectal cancer, in combination with intravenous fluorouracilbased chemotherapy for first- or second-line treatment.2.Metastatic colorectal cancer, in combination with fluoropyrimidineirinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line Avastin-containing regimen.Limitations of Use: Avastin is not indicated for adjuvant treatment of colon cancer.3.Unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment.4. Recurrent glioblastoma in adults.5.Metastatic renal cell carcinoma in combination with interferon alfa.6.Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan.7.Epithelial ovarian, fallopian tube, or primary peritoneal cancer:(1) in combination with carboplatin and paclitaxel, followed by Avastin as a single agent, for stage III or IV disease following initial surgical resection.(2)in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens.(3)in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by Avastin as a single agent, for platinumsensitive recurrent disease.8.Hepatocellular Carcinoma (HCC). Avastin是一种血管内皮生长因子抑制剂，其适应症为：1.与基于氟尿嘧啶的静脉化疗联合用于转移性结直肠癌的一线或二线治疗。2.与基于氟嘧啶-伊立替康或氟嘧啶-奥沙利铂的化疗联合用于含Avastin一线方案治疗后疾病进展的转移性结直肠癌的二线治疗。3.与卡铂、紫杉醇联合用于不可切除的、局部晚期、复发性或转移性非鳞状非小细胞肺癌的一线治疗。4.成人复发性胶质母细胞瘤。5.联合干扰素α用于治疗转移性肾细胞癌。6.与紫杉醇、顺铂或紫杉醇、拓扑替康联合，用于治疗持续性、复发性或转移性宫颈癌。7.上皮性卵巢癌、输卵管癌或原发性腹膜癌：(1)与卡铂和紫杉醇联合，然后使用Avastin单药，用于治疗首次手术切除后的III期或IV期疾病。(2)与紫杉醇、聚乙二醇脂质体多柔比星或拓扑替康联合，用于治疗既往接受不超过2个化疗方案的铂耐复发性疾病。(3)与卡铂、紫杉醇或卡铂、吉西他滨联合，然后使用Avastin单药，用于治疗铂敏感复发性疾病。8.与Atezolizumab联合用于治疗既往未接受过全身治疗的不可切除或转移性肝细胞癌(HCC)患者。2020年NMPA批准用于转移性结直肠癌患者的治疗。2.非鳞状细胞非小细胞肺癌患者的治疗。3.成人复发性胶质母细胞瘤患者的治疗。2021年NMPA批准治疗肝细胞癌患者.贝伐珠单抗联合卡铂和紫杉醇用于初次手术切除后的III 期或 IV 期上皮性卵巢癌、输卵管癌或原发性腹膜癌患者的一线治疗。2021年11月NMPA批准用于宫颈癌患者的治疗。 结直肠癌、非小细胞肺癌、胶质母细胞瘤、肾癌、宫颈癌、上皮性卵巢癌、输卵管癌、原发性腹膜癌、肝癌 Bevacizumab products bind VEGF and prevent the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis. Administration of bevacizumab to xenotransplant models of colon cancer in nude (athymic) mice caused reduction of microvascular growth and inhibition of metastatic disease progression. Bevacizumab结合VEGF并阻止VEGF与其内皮细胞表面的受体(Flt-1和KDR)相互作用。在体外血管生成模型中，VEGF与其受体的相互作用导致内皮细胞增殖和<E6AE96>
Bevacizumab-bvzr 贝伐珠单抗-bvzr Zirabev 辉瑞 2019/6/27 FDA ZIRABEV is a vascular endothelial growth factor inhibitor indicated for the treatment of: 1.Metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment. 2.Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen.3.Unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment. 4.Recurrent glioblastoma in adults.5.Metastatic renal cell carcinoma in combination with interferon alfa. 6.Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan. 7.Epithelial ovarian, fallopian tube, or primary peritoneal cancer:（1）in combination with carboplatin and paclitaxel, followed by ZIRABEV as a single agent, for stage III or IV disease following initial surgical resection. （2）in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens. （3）in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by ZIRABEV as a single agent, for platinum-sensitive recurrent disease. ZIRABEV是一种血管内皮生长因子抑制剂，其适应症为：1.与基于氟尿嘧啶的静脉化疗联合用于转移性结直肠癌的一线或二线治疗。2.与基于氟嘧啶-伊立替康或氟嘧啶-奥沙利铂的化疗联合用于含ZIRABEV一线方案治疗后疾病进展的转移性结直肠癌的二线治疗。3.与卡铂、紫杉醇联合用于不可切除的、局部晚期、复发性或转移性非鳞状非小细胞肺癌的一线治疗。4.成人复发性胶质母细胞瘤。5.联合干扰素α用于治疗转移性肾细胞癌。6.与紫杉醇、顺铂或紫杉醇、拓扑替康联合，用于治疗持续性、复发性或转移性宫颈癌。7.上皮性卵巢癌、输卵管癌或原发性腹膜癌：(1)与卡铂和紫杉醇联合，然后使用ZIRABEV单药，用于治疗首次手术切除后的III期或IV期疾病。(2)与紫杉醇、聚乙二醇脂质体多柔比星或拓扑替康联合，用于治疗既往接受不超过2个化疗方案的铂耐复发性疾病。(3)与卡铂、紫杉醇或卡铂、吉西他滨联合，然后使用ZIRABEV单药，用于治疗铂敏感复发性疾病。 结直肠癌、非小细胞肺癌、胶质母细胞瘤、肾癌、宫颈癌、上皮性卵巢癌、输卵管癌、原发性腹膜癌 Bevacizumab products bind VEGF and prevent the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis. Administration of bevacizumab to xenotransplant models of colon cancer in nude (athymic) mice caused reduction of microvascular growth and inhibition of metastatic disease progression. Bevacizumab结合VEGF并阻止VEGF与其内皮细胞表面的受体(Flt-1和KDR)相互作用。在体外血管生成模型中，VEGF与其受体的相互作用导致内皮细胞增殖和新血管形成。在裸鼠结肠癌异种移植模型中给予贝伐单抗，导致微血管生长减少和转移疾病进展的抑制。 02/2021 2021/11/26 pj/sjz D0023
Bevacizumab-awwb 贝伐珠单抗-awwb Mvasi 安进 2017/9/14 FDA MVASI is a vascular endothelial growth factor inhibitor indicated for the treatment of: 1.Metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment. 2.Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen.3.Unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment. 4.Recurrent glioblastoma in adults.5.Metastatic renal cell carcinoma in combination with interferon alfa. 6.Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan. 7.Epithelial ovarian, fallopian tube, or primary peritoneal cancer:（1）in combination with carboplatin and paclitaxel, followed by MVASI as a single agent, for stage III or IV disease following initial surgical resection. （2）in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens. （3）in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by MVASI as a single agent, for platinum-sensitive recurrent disease. MVASI是一种血管内皮生长因子抑制剂，其适应症为：1.与基于氟尿嘧啶的静脉化疗联合用于转移性结直肠癌的一线或二线治疗。2.与基于氟嘧啶-伊立替康或氟嘧啶-奥沙利铂的化疗联合用于含MVASI一线方案治疗后疾病进展的转移性结直肠癌的二线治疗。3.与卡铂、紫杉醇联合用于不可切除的、局部晚期、复发性或转移性非鳞状非小细胞肺癌的一线治疗。4.成人复发性胶质母细胞瘤。5.联合干扰素α用于治疗转移性肾细胞癌。6.与紫杉醇、顺铂或紫杉醇、拓扑替康联合，用于治疗持续性、复发性或转移性宫颈癌。7.上皮性卵巢癌、输卵管癌或原发性腹膜癌：(1)与卡铂和紫杉醇联合，然后使用MVASI单药，用于治疗首次手术切除后的III期或IV期疾病。(2)与紫杉醇、聚乙二醇脂质体多柔比星或拓扑替康联合，用于治疗既往接受不超过2个化疗方案的铂耐复发性疾病。(3)与卡铂、紫杉醇或卡铂、吉西他滨联合，然后使用MVASI单药，用于治疗铂敏感复发性疾病。 结直肠癌、非小细胞肺癌、胶质母细胞瘤、肾癌、宫颈癌、上皮性卵巢癌、输卵管癌、原发性腹膜癌 Bevacizumab products bind VEGF and prevent the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis. Administration of bevacizumab to xenotransplant models of colon cancer in nude (athymic) mice caused reduction of microvascular growth and inhibition of metastatic disease progression. Bevacizumab结合VEGF并阻止VEGF与其内皮细胞表面的受体(Flt-1和KDR)相互作用。在体外血管生成模型中，VEGF与其受体的相互作用导致内皮细胞增殖和新血管形成。在裸鼠结肠癌异种移植模型中给予贝伐单抗，导致微血管生长减少和转移疾病进展的抑制。 11/2021 2021/11/26 pj/sjz D0024
Infigratinib Truseltiq HelsinnHealthcare SA 2021/5/28 FDA TRUSELTIQ is a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. TRUSELTIQ是一种激酶抑制剂，适用于先前接受过治疗、携带FGFR2融合或重排的不可切除性局部晚期或转移性胆管癌成人患者。 胆管癌 Infigratinib is a small molecule kinase inhibitor of FGFR with IC50 values of 1.1, 1, 2, and 61 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively. The major human metabolites of infigratinib, BHS697 and CQM157, have similar in vitro binding affinities for FGFR1, FGFR2, and FGFR3 compared to infigratinib. Infigratinib inhibited FGFR signaling and decreased cell proliferation in cancer cell lines with activating FGFR amplifications, mutations, or fusions. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Infigratinib had anti-tumor activity in mouse and rat xenograft models of human tumors with activating FGFR2 or FGFR3 alterations, including two patient-derived xenograft models of cholangiocarcinoma that expressed FGFR2-TTC28 or FGFR2-TRA2B fusions. Infigratinib demonstrated brain-to-plasma concentration ratios (based on AUC0-inf) of 0.682 in rats after a single oral dose. Infiglatinib是FGFR的小分子激酶抑制剂，对FGFR1、FGFR2、FGFR3和FGFR4的IC50值分别为1.1、1、2和61 nM。与Infiglatinib相比，Infiglatinib的主要人体代谢物BHS697和CQM157对FGFR1、FGFR2和FGFR3具有相似的体外结合亲和力。在激活的FGFR扩增、突变或融合的癌细胞系中，Infiglatinib抑制FGFR信号传导并降低细胞增殖。组成性FGFR信号可以支持恶性细胞的增殖和存活。Infiglatinib在具有FGFR2或FGFR3激活变异的人源肿瘤小鼠和大鼠异种移植模型中具有抗肿瘤活性，包括两种表达FGFR2-TTC28或FGFR2-TRA2B融合的胆管癌患者源性异种移植模型。单次口服Infigratinib后，大鼠的脑-血浆浓度比(基于AUC0-inf)为0.682。 05/2021 2021/11/26 D0025
Binimetinib 贝美替尼 Mektovi Array BioPharma Inc 2018/6/27 0:00 FDA MEKTOVI is a kinase inhibitor indicated:· in combination with encorafenib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. · in combination with encorafenib, for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test. MEKTOVI是一种激酶抑制剂，联合康奈非尼用于治疗BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。2023年10月11日，FDA批准新适应症为：联合康奈非尼用于治疗携带BRAF V600E突变的转移性非小细胞肺癌（NSCLC）成人患者。 黑色素瘤 Binimetinib is a reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. In vitro, binimetinib inhibited extracellular signal-related kinase (ERK) phosphorylation in cell- free assays as well as viability and MEK-dependent phosphorylation of BRAF-mutant human melanoma cell lines. Binimetinib also inhibited in vivo ERK phosphorylation and tumor growth in BRAF-mutant murine xenograft models.Binimetinib and encorafenib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared to either drug alone, coadministration of encorafenib and binimetinib resulted in greater anti-proliferative activity in vitro in BRAF mutation-positive cell lines and greater anti-tumor activity with respect to tumor growth inhibition in BRAF V600E mutant human melanoma xenograft studies in mice. Additionally, the combination of binimetinib and encorafenib delayed the emergence of resistance in BRAF V600E mutant human melanoma xenografts in mice compared to either drug alone. 贝美替尼(Binimetinib)是一种有丝分裂原激活的细胞外信号调节激酶1（MEK1）和MEK2活性的可逆抑制剂。MEK蛋白是细胞外信号相关激酶（ERK）途径的上游调控蛋白。在体外，贝美替尼(Binimetinib)在非细胞试验中能抑制细胞外信号相关激酶(ERK)的磷酸化，并抑制了BRAF突变型人黑素瘤细胞系的活力和MEK依赖性磷酸化。在BRAF突变的小鼠异种移植瘤模型中，贝美替尼(Binimetinib)也能抑制体内ERK磷酸化和肿瘤生长。贝美替尼(Binimetinib)和康奈非尼(Encorafenib)靶向RAS/RAF/MEK/ERK通路的两种不同激酶。与单独使用任何一种药物相比，康奈非尼(Encorafenib)和贝美替尼(Binimetinib)联合用药在体外对BRAF突变阳性细胞系产生更强的抗增殖活性，且在BRAF V600E突变型人类黑色素瘤小鼠异种移植研究中，对肿瘤生长抑制显示出更强的抗肿瘤活性。此外，与单独使用两种药物相比，联合使用贝美替尼(Binimetinib)和康奈非尼(Encorafenib)延缓了BRAF V600E突变型人黑色素瘤小鼠异种移植瘤模型耐药性的出现。 10/2023 231013 pj D0026 适应症更新 SXZ
Bosutinib 博舒替尼 Bosulif 辉瑞 2012/9/4 FDA BOSULIF is a kinase inhibitor indicated for the treatment of adult patients with Newly-diagnosed chronic phase Ph+ chronic myelogenous leukemia (CML). This indication is approved under accelerated approval based on molecular and cytogenetic response rates. Continued approval for this indication may be contingent upon verification and confirmation of clinical benefit in an ongoing long-term follow up trial. Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy. BOSULIF是一种激酶抑制剂，适用于新诊为慢性期Ph+慢性髓系白血病(CML)、或对先前治疗耐药或不耐受的慢性期、加速期或母细胞期Ph+ CML成人患者。 慢性髓系白血病 Bosutinib is a TKI. Bosutinib inhibits the BCR-ABL kinase that promotes CML; it is also an inhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms of BCR-ABL kinase expressed in murine myeloid cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells. 博舒替尼(Bosutinib)是一种酪氨酸激酶抑制剂。博舒替尼(Bosutinib)不仅能抑制促慢性粒细胞白血病发生的BCR-ABL激酶活性，也是Src家族激酶（包括Src，Lyn和Hck）的抑制剂。小鼠骨髓细胞系中表达的18种伊马替尼(Imatinib)耐药BCR-ABL激酶变体中有16种可被博舒替尼(Bosutinib)抑制。博舒替尼(Bosutinib)对T315I和V299L突变细胞没有抑制作用。 05/2021 2021/11/26 D0027
Brigatinib 布格替尼 Alunbrig TakedaPharmsUSA 2017/4/28 FDA ALUNBRIG is a kinase inhibitor indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. ALUNBRIG是一种激酶抑制剂，适用于间变性淋巴瘤激酶(ALK)阳性的转移性非小细胞肺癌(NSCLC)成人患者。 非小细胞肺癌 Brigatinib is a tyrosine kinase inhibitor with in vitro activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays. Brigatinib also inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice.At clinically achievable concentrations (≤500 nM), brigatinib inhibited the in vitro viability of cells expressing EML4-ALK and 17 mutant forms associated with resistance to ALK inhibitors including crizotinib, as well as EGFR-Del (E746-A750), ROS1-L2026M, FLT3-F691L, and FLT3-D835Y. Brigatinib exhibited in vivo antitumor activity against 4 mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib.Brigatinib also reduced tumor burden and prolonged survival in mice implanted intracranially with an ALK-driven tumor cell line. 布格替尼(Brigatinib)是一种酪氨酸激酶抑制剂，体外浓度达到临床相关浓度时可以抑制多种激酶的活性，包括ALK、ROS1、胰岛素样生长因子1受体（IGF-1R）和FLT-3以及EGFR缺失和点突变。在体外和体内试验中，布格替尼(Brigatinib)能抑制ALK的自磷酸化以及ALK介导的下游信号蛋白STAT3、AKT、ERK1/2和S6的磷酸化。布格替尼(Brigatinib)还抑制了表达EML4-ALK和NPM-ALK融合蛋白细胞系的体外增殖，并显示出对EML4-ALK阳性、非小细胞肺癌小鼠异种移植瘤模型生长的剂量依赖性抑制作用。在临床相关浓度(≤500nM)下，布格替尼(Brigatinib)抑制了表达EML4-ALK和17种与ALK抑制剂（包括克唑替尼Crizotinib）耐药相关突变细胞的体外活力，这些突变包括EGFR-Del (E746-A750)、ROS1-L2026M、FLT3-F691L和FLT3-D835Y。布格替尼(Brigatinib)还对4种EML4-ALK突变表现出体内抗肿瘤活性，包括在克唑替尼(Crizotinib)治疗后疾病进展的NSCLC患者中发现的G1202R和L1196M突变。布格替尼(Brigatinib)还可减轻颅内植入ALK驱动肿瘤细胞系小鼠的肿瘤负担，并延长其生存期。 09/2021 2021/11/26 D0028
Buparlisib Buparlisib has been used in trials studying the treatment and basic science of Lymphoma, Metastases, Lung Cancer, Solid Tumors, and Breast Cancer, among others. Buparlisib (BKM120; NVP-BKM120) 是一种 pan-class I PI3K 抑制剂，作用于 p110α/p110β/p110δ/p110γ，IC50 分别为 52 nM/166 nM/116 nM/262 nM。 Buparlisib已用于研究淋巴瘤、转移瘤、肺癌、实体瘤和乳腺癌等疾病的治疗和基础科学的试验中。 230928 pj D0029 新增作用机制内容 LXL
Cabozantinib 卡博替尼 Cabometyx/COMETRIQ Exelixis 2012 FDA CABOMETYX is a kinase inhibitor indicated for the treatment of .1.patients with advanced renal cell carcinoma (RCC) . 2.patients with advanced renal cell carcinoma, as a first-line treatment in combination with nivolumab. 3.patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib . 4.adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible .COMETRIQ is a kinase inhibitor indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC). CABOMETYX是一种激酶抑制剂，其适应症为：1. 晚期肾癌( RCC )患者。2. 联合尼伐单抗进行晚期肾癌的一线治疗。3.既往曾使用索拉非尼的肝细胞癌( HCC )患者。 4. 既往接受过VEGFR靶向治疗的进展期放射性碘难治性局部晚期或转移性分化型甲状腺癌( DTC )的（年龄12岁以上）的成人和儿童患者。COMETRIQ是一种激酶抑制剂，用于治疗进展性、转移性甲状腺髓样癌(MTC)患者。 肾癌、肝癌、甲状腺癌 In vitro biochemical and/or cellular assays have shown that cabozantinib inhibits the tyrosine kinase activity of RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, ROS1, TYRO3, MER, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment. 体外生化和/或细胞分析研究表明，卡博替尼(Cabozantinib)抑制RET、MET、VEGFR-1、VEGFR-2和VEGFR-3、KIT、TRKB、FLT-3、AXL、ROS1、TYRO3、MER和TIE-2的酪氨酸激酶活性。这些酪氨酸激酶受体涉及参与调控细胞正常功能和病理进程（如肿瘤发生、转移、肿瘤血管生成、耐药发生和肿瘤微环境维持）。 07/2022 2023/5/10 0:00 sxz D0030 商品名修改 LXL
Capmatinib 卡马替尼 Tabrecta 诺华制药 2020/5/6 FDA TABRECTA is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. TABRECTA是一种激酶抑制剂，适用于携带间质表皮转化因子(MET)基因14号外显子跳跃突变的转移性非小细胞肺癌(NSCLC)成人患者。 非小细胞肺癌 Capmatinib is a kinase inhibitor that targets MET, including the mutant variant produced by exon 14 skipping. MET exon 14 skipping results in a protein with a missing regulatory domain that reduces its negative regulation leading to increased downstream MET signaling. Capmatinib inhibited cancer cell growth driven by a mutant MET variant lacking exon 14 at clinically achievable concentrations and demonstrated anti-tumor activity in murine tumor xenograft models derived from human lung tumors with either a mutation leading to MET exon 14 skipping or MET amplification. Capmatinib inhibited the phosphorylation of MET triggered by binding of hepatocyte growth factor or by MET amplification, as well as MET- mediated phosphorylation of downstream signaling proteins and proliferation and survival of MET-dependent cancer cells. 卡马替尼（Capmatinib）是一种针对MET的激酶抑制剂，这其中就包括外显子14跳跃产生的突变。MET外显子14跳跃会导致蛋白质缺失调控域，从而降低其负调控，导致下游MET信号传导增加。卡马替尼（Capmatinib）在临床相关浓度下可抑制MET 14号外显子缺失突变驱动的肿瘤细胞生长，并在小鼠人源肺癌异种移植模型中显示出抗肿瘤活性，该模型的基因突变会导致MET 14号外显子跳跃或MET扩增。卡马替尼(Capmatinib)抑制由肝细胞生长因子结合或MET扩增触发的MET磷酸化，以及MET介导的下游信号蛋白磷酸化和MET依赖性肿瘤细胞的增殖和存活。 05/2020 2021/11/26 D0031
Cemiplimab-rwlc Libtayo 再生元制药 2018/9/28 FDA LIBTAYO is a programmed death receptor-1 (PD-1) blocking antibody indicated:1.Cutaneous Squamous Cell Carcinoma (CSCC): for the treatment of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation. 2.Basal Cell Carcinoma (BCC):(1) for the treatment of patients with locally advanced BCC (laBCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. （2） for the treatment of patients with metastatic BCC (mBCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. 3.Non-Small Cell Lung Cancer (NSCLC):for the first-line treatment of patients with NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥ 50%] , with no EGFR, ALK or ROS1 aberrations, and is locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or metastatic. LIBTAYO是一种程序性死亡受体-1 (PD-1)阻断抗体，其适应症为：1.用于治疗不适合手术或放疗的转移性或局部晚期的皮肤鳞状细胞癌(CSCC)患者。2.用于治疗既往接受过Hedgehog信号通路抑制剂或Hedgehog信号通路抑制剂不适用的转移性或局部晚期的基底细胞癌(BCC)患者。3.用于以下PD-L1高表达[ 肿瘤比例评分(TPS)≥ 50%]，且无EGFR、ALK或ROS1异常的非小细胞肺癌(NSCLC)患者的一线治疗：(1)不适合手术或根治性放化疗的局部晚期的NSCLC患者；(2)转移性NSCLC患者。 皮肤鳞状细胞癌，基底细胞癌，非小细胞肺癌 Binding of the programmed death receptor (PD) ligands PD-L1 and PD-L2, to the PD-1 receptor, which is found on T cells, inhibits T-cell proliferation and cytokine production. The upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway may contribute to the inhibition of active T-cell immune surveillance of tumors. Cemiplimab is a recombinant human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2 ligands, causing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In mouse tumor models, blocking PD-1 activity resulted in decreased rates of tumor growth. 程序性死亡受体（PD）的配体PD-L1和PD-L2与T细胞上PD-1受体的结合会抑制T细胞增殖和细胞因子的产生。某些肿瘤中会发生PD-1配体的上调，通过该途径的信号传导有助于肿瘤逃避活化T细胞的免疫监视。Cemiplimab是一种人类免疫球蛋白G4（IgG4）单克隆抗体，与PD-1受体结合并阻断其与PD-L1和PD-L2的相互作用，从而解除PD-1途径介导的免疫应答抑制作用，包括抗肿瘤免疫反应。在小鼠肿瘤模型中，阻断PD-1活性可以降低肿瘤生长速率。 02/2021 2021/11/26 pj/sjz D0033
Ceritinib 赛瑞替尼 Zykadia 赞可达 诺华制药 2018/10/31 FDA/NMPA ZYKADIA is a kinase inhibitor indicated for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. ZYKADIA是一种激酶抑制剂，适用于间变性淋巴瘤激酶(ALK)阳性的转移性非小细胞肺癌(NSCLC)。2018年NMPA批准赛瑞替尼药适用于非小细胞肺癌（NSCLC）患者的治疗。 非小细胞肺癌 Ceritinib is a kinase inhibitor. Targets of ceritinib inhibition identified in either biochemical or cellular assays at clinically relevant concentrations include ALK, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. Among these, ceritinib is most active against ALK. Ceritinib inhibited autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells in in vitro and in vivo assays.Ceritinib inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice and rats. Ceritinib exhibited dose-dependent anti-tumor activity in mice bearing EML4-ALK-positive NSCLC xenografts with demonstrated resistance to crizotinib, at concentrations within a clinically relevant range. 色瑞替尼(Ceritinib)是一种激酶抑制剂。达到临床相关浓度的生化或细胞分析中，色瑞替尼(Ceritinib)抑制作用的靶点包括ALK、胰岛素样生长因子1受体(IGF-1R)、胰岛素受体(InsR)和ROS1。其中，色瑞替尼(Ceritinib)对ALK的活性最高。在体外和体内试验中，色瑞替尼(Ceritinib)可抑制ALK的自磷酸化，ALK介导的下游信号蛋白STAT3的磷酸化，以及ALK依赖性肿瘤细胞的增殖。色瑞替尼(Ceritinib)在体外实验中能抑制表达EML4-ALK和NPM-ALK融合蛋白细胞系的增殖，对小鼠和大鼠中EML4-ALK阳性非小细胞肺癌（NSCLC）异种移植瘤的生长表现出剂量依赖性抑制作用。在EML4-ALK阳性NSCLC小鼠异种移植瘤对克唑替尼(Crizotinib)耐药的情况下,色瑞替尼(Ceritinib)在临床相关浓度范围内显示出剂量依赖的抗肿瘤活性。 FDA-approval:10/2021;NMPA-approval:2018 2023/6/20 sxz D0034 修改日期；sxz
Cetuximab 西妥昔单抗 Erbitux 爱必妥 默克 2004/2/12 FDA/NMPA ERBITUX is an epidermal growth factor receptor (EGFR) antagonist indicated for treatment of: 1.Locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. 2. Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil. 3.Recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy. 4. K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test. in combination with FOLFIRI for first-line treatment. 5.in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy. 6.as a single-agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan. 7. BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC): in combination with encorafenib, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy. ERBITUX是一种表皮生长因子受体(EGFR)拮抗剂，其适应症包括：1.联合放疗用于治疗局部或区域晚期头颈鳞癌。2.联合铂类和氟尿嘧啶用于治疗头颈部复发性局部疾病或转移性头颈鳞癌。3.铂类治疗后进展的复发性或转移性头颈鳞癌。4.联合FOLFIRI用于K-Ras野生型、EGFR表达阳性的转移性结直肠癌的一线治疗。5.联合伊立替康用于治疗对基于伊立替康化疗耐药的K-Ras野生型、EGFR表达阳性的转移性结直肠癌患者。6.单药用于治疗对奥沙利铂和伊立替康为基础的化疗失败或对伊立替康不耐受的K-Ras野生型、EGFR表达阳性的转移性结直肠癌患者。7.联合康奈非尼用于先前治疗后携带BRAF V600E突变的转移性结直肠癌(CRC)成人患者。2019年NMPA批准西妥昔单抗用于治疗 RAS 基因野生型的转移性结直肠癌：与 FOLFOX 或 FOFIRI 方案联合用于一线治疗。与伊立替康联合用于经含伊立替康治疗失败后的患者。2019年NMPA批准西妥昔单抗与铂类和氟尿嘧啶化疗联合用于一线治疗复发和/或转移性疾病头颈部鳞状细胞癌。2022年NMPA批准西妥昔单抗与放疗联合用于治疗局部晚期头颈部鳞状细胞癌。 头颈癌、结直肠癌 The epidermal growth factor receptor (EGFR, HER1, c-ErbB-1) is a transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine kinases including EGFR, HER2, HER3, and HER4. The EGFR is constitutively expressed in many normal epithelial tissues, including the skin and hair follicle. Expression of EGFR is also detected in many human cancers including those of the head and neck, colon, and rectum.Cetuximab binds specifically to the EGFR on both normal and tumor cells, and competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor-alpha. In vitro assays and in vivo animal studies have shown that binding of cetuximab to the EGFR blocks phosphorylation and activation of receptor- associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased matrix metalloproteinase and vascular endothelial growth factor production. Signal transduction through the EGFR results in activation of wild-type Ras proteins, but in cells with activating Ras somatic mutations, the resulting mutant Ras proteins are continuously active regardless of EGFR regulation.In vitro, cetuximab can mediate antibody-dependent cellular cytotoxicity (ADCC) against certain human tumor types. In vitro assays and in vivo animal studies have shown that cetuximab inhibits the growth and survival of tumor cells that express the EGFR. No anti-tumor effects of cetuximab were observed in human tumor xenografts lacking EGFR expression. The addition of cetuximab to radiation therapy or irinotecan in human tumor xe
Cobimetinib 考比替尼 Cotellic 基因泰克 2015/11/10 FDA COTELLIC is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib. COTELLIC是一种激酶抑制剂，其适应症为联合维莫非尼用于治疗携带BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。 黑色素瘤 Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1 (MEK1) and MEK.2. MEK proteins are upstream regulators of the extracellular signal- related kinase (ERK) pathway, which promotes cellular proliferation. BRAF V600E and K mutations result in constitutive activation of the BRAF pathway which includes MEK1 and MEK2. In mice implanted with tumor cell lines expressing BRAF V600E, cobimetinib inhibited tumor cell growth.Cobimetinib and vemurafenib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared to either drug alone, coadministration of cobimetinib and vemurafenib resulted in increased apoptosis in vitro and reduced tumor growth in mouse implantation models of tumor cell lines harboring BRAF V600E mutations. Cobimetinib also prevented vemurafenib-mediated growth enhancement of a wild-type BRAF tumor cell line in an in vivo mouse implantation model. 考比替尼(Cobimetinib)是一种靶向有丝分裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶1（MEK1）和MEK2的可逆抑制剂。MEK蛋白是细胞外信号调节激酶(ERK)通路的上游调控蛋白，该通路可促进细胞增殖。BRAF V600E和K突变导致包括MEK1和MEK2在内的BRAF途径的组成性激活。在移植表达BRAF V600E肿瘤细胞系的小鼠中，考比替尼(Cobimetinib)抑制了肿瘤细胞的生长。考比替尼(Cobimetinib)和维罗非尼(Vemurafenib)靶向RAS/RAF/MEK/ERK通路的两种不同激酶。与单独使用这两种药物相比，考比替尼(Cobimetinib)和维罗非尼(Vemurafenib)联合用药在体外可增加细胞凋亡，在植入表达BRAF V600E突变的肿瘤细胞系的小鼠中可抑制肿瘤生长。此外,在小鼠肿瘤细胞移植模型中,考比替尼(Cobimetinib)还可以阻止维罗非尼(Vemurafenib)介导的野生型BRAF肿瘤细胞系的生长。 01/2018 2021/11/26 D0037
Copanlisib 可泮利塞 Aliqopa 奥罗巴 Bayer HealthCare Pharmaceuticals Inc. 2017/9/14 0:00 FDA/NMPA ALIQOPA is a kinase inhibitor indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies ALIQOPA是一种激酶抑制剂，适用于既往至少接受过两次全身治疗的复发滤泡状淋巴瘤(FL)成人患者。 淋巴瘤 Follicular lymphoma is a B-cell lymphoma that is one of the most common type of non-Hodgkin lymphoma (NHL). It involves unregulated growth and proliferation of lymphocytes that eventually may travel to other organs including the lymph nodes, spleen, and the bone marrow, to form tumors. The phosphatidylinositol 3-kinase (PI3K)-mediated pathway is involved in promoting cell survival proliferation and differentiation however abberant activation of this pathway may lead to tumorigenesis(PubMed:27672108). Copanlisib mediates an inhibitory action on p110α and p110δ isoforms of phosphatidylinositol-3-kinase (PI3K) expressed in malignant B cells. It induces tumor cell death via apoptosis and inhibits the proliferation of primary malignant B cell lines. Copanlisib inhibits several key cell-signaling pathways, including B-cell receptor (BCR) signaling, CXCR12 mediated chemotaxis of malignant B cells, and NFκB signaling in lymphoma cell lines. 滤泡性淋巴瘤是一种B细胞淋巴瘤，是最常见的非霍奇金淋巴瘤（NHL）类型之一。 它涉及淋巴细胞的失控生长和增殖，最终可能传播到其他器官，包括淋巴结、脾脏和骨髓，从而形成肿瘤。 磷脂酰肌醇3-激酶（PI3K）介导的信号途径参与促进细胞存活增殖和分化，但是该途径的异常激活可能导致肿瘤发生（PubMed: 27672108）。Copanlisib介导对恶性B细胞中表达的磷脂酰肌醇3-激酶（PI3K）p110α和p110δ两种亚型的抑制作用。Copanlisib通过凋亡诱导肿瘤细胞死亡并抑制原发性恶性B细胞系的增殖。Copanlisib还可以抑制几种关键的细胞信号通路，包括B细胞受体（BCR）信号转导，CXCR12介导的恶性B细胞趋化性和淋巴瘤细胞系中的NFκB信号转导。 02/2020 2023/5/26 0:00 SXZ D0038 批准单位更新 LXL
Crenolanib Crenolanib is under investigation for the treatment of Diffuse Intrinsic Pontine Glioma and Progressive or Refractory High-Grade Glioma. Crenolanib 是有效和选择性的野生型和突变型 III 类受体酪氨酸激酶抑制剂，抑制 FLT3 和 PDGFRα/β 的 Kd 分别为 0.74 nM，2.1 nM，3.2 nM。 Crenolanib正用于研究弥漫性内源性庞廷胶质瘤和进行性或难治性高级别胶质瘤的治疗。 231008 pj D0039 新增作用机制内容 LXL
Crizotinib 克唑替尼 Xalkori 赛可瑞 PFPrismCV 2011/8/26 FDA/NMPA Crizotinib is a kinase inhibitor indicated for the treatment of：1.patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test.2.pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive( Limitations of Use: The safety and efficacy of XALKORI have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL).2. adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive. 克唑替尼是一种激酶抑制剂，其适应症为：1.间变性淋巴瘤激酶(ALK)或ROS1阳性的转移性非小细胞肺癌(NSCLC)患者。2.复发性或难治性的系统性ALK阳性间变性大细胞淋巴瘤(ALCL)的 1 岁及以上儿童患者和青少年患者(使用限制:克唑替尼对复发或难治性系统性ALK阳性间变性大细胞淋巴瘤(ALCL)老年人的安全性和有效性尚未得到证实)。3.不可切除、复发或难治性1岁及以上ALK阳性的炎症性肌纤维母细胞瘤(IMT)的成人和儿童患者。2013年NMPA批准克唑替尼胶囊可用于间变性淋巴瘤激酶（ALK）阳性的局部晚期或转移性非小细胞肺癌（NSCLC）患者的治疗。2017年NMPA批准克唑替尼胶囊可用于 ROS1 阳性的晚期非小细胞肺癌（NSCLC）患者的治疗. 非小细胞肺癌、间变性大细胞淋巴瘤、炎症性肌纤维母细胞瘤 Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d’Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene’s expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins. Crizotinib demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed echinoderm microtubule-associated protein-like 4 (EML4)- or nucleophosmin (NPM)-ALK fusion proteins or c-Met. 克唑替尼(Crizotinib)是一种酪氨酸激酶受体抑制剂，对应靶点包括ALK、肝细胞生长因子受体（HGFR，c-Met)、ROS1(c-cos)和Recepteur d'Origine Nantais (RON)。ALK基因易位可引起致癌融合蛋白的表达。ALK融合蛋白的形成导致基因表达和信号转导的激活和失调，可以促进表达这些蛋白的肿瘤细胞的增殖和存活。克唑替尼(Crizotinib)在使用肿瘤细胞系的细胞实验中显示出对ALK、ROS1和c-Met磷酸化的浓度依赖性抑制作用，并且在表达棘皮动物微管相关蛋白4（EML4）或核磷蛋白（NPM）-ALK融合蛋白或c-Met的肿瘤移植小鼠中显示出抗肿瘤活性。 FDA-approval:07/2022;NMPA-approval:2017 2023/6/20 sxz D0040 适应症修改
Dabrafenib 达拉非尼 Tafinlar 泰菲乐 诺华制药 2013/5/29 0:00 FDA/NMPA TAFINLAR is a kinase inhibitor indicated 1.as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. 2.TAFINLAR is indicated, in combination with trametinib, for: （1）the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.（2）the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. （3）the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.（4）the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options.（5）the treatment of adult and pediatric patients 6 years of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)。TAFINLAR is not indicated for treatment of patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition. TAFINLAR is not indicated for treatment of patients with wild-type BRAF solid tumors. TAFINLAR是一种激酶抑制剂，其适应症为：1.单药用于治疗BRAF V600E突变的不可切除性或转移性黑色素瘤。2.联合曲美替尼用于：(1)BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。(2)BRAF V600E或V600K突变、手术切除后累及淋巴结的黑色素瘤的辅助治疗。(3)BRAF V600E突变的转移性非小细胞肺癌(NSCLC)。(4)BRAF V600E突变且没有令人满意的局部治疗选择的局部晚期或转移性间变性甲状腺癌(ATC)。（5）适用于携带BRAF V600突变的不可切除或转移性6岁及以上的成人和儿童实体瘤患者，且这些患者在之前的治疗后进展且没有合适的替代治疗方案。(6)携带BRAF V600E突变需要全身治疗的儿童（1岁及以上)低级别胶质瘤（LCG)患者 备注：BRAF抑制具有耐药性，因此TAFINLAR不用于结直肠癌患者的治疗，TAFINLAR也不适用于野生型BRAF实体瘤的治疗。使用限制:TAFINLAR不用于结直肠癌患者的治疗，因为已知的BRAF抑制内在耐药(1.7,12.1)。TAFINLAR不适用于野生型BRAF实体瘤的治疗.2019年NMPA批准达拉非尼于治疗 BRAF V600 突变阳性的不可切除或转移性黑色素瘤患者，联合曲美替尼适用于 BRAF V600 突变阳性的III期黑色素瘤患者完全切除后的辅助治疗。2022年NMPA批准达拉非尼联合曲美替尼适用于治疗 BRAF V600 突变阳性的转移性非小细胞肺癌患者。 黑色素瘤、非小细胞肺癌、甲状腺癌 Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM, respectively, and other kinases, such as SIK1, NEK11, and LIMK1 at higher concentrations. Some mutations in the BRAF gene, including those that result in BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth [see Indications and Usage (1)]. Dabrafenib inhibits cell growth of various BRAF V600 mutation- positive tumors in vitro and in vivo.Dabrafenib and trametinib target two different kinases in the RAS/RAF/MEK/ERK pathway. Use of dabrafenib and trametinib in combination resulted in greater growth inhibition of BRAF V600 mutation-positive tumo
Dacomitinib 达可替尼 Vizimpro 多泽润 PfizerEuropeMAEEIG 2018/12/10 FDA/NMPA VIZIMPRO is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test. VIZIMPRO是一种激酶抑制剂，适用于表皮生长因子受体(EGFR)19号外显子缺失或21号外显子L858R置换突变的转移性非小细胞肺癌(NSCLC)的一线治疗。2019年NMPA批准用于非小细胞肺癌（NSCLC）患者的治疗。 非小细胞肺癌 Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR family (EGFR/HER1, HER2, and HER4) and certain EGFR activating mutations (exon 19 deletion or the exon 21 L858R substitution mutation). In vitro dacomitinib also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 at clinically relevant concentrations.Dacomitinib demonstrated dose-dependent inhibition of EGFR and HER2 autophosphorylation and tumor growth in mice bearing subcutaneously implanted human tumor xenografts driven by HER family targets including mutated EGFR. Dacomitinib also exhibited antitumor activity in orally-dosed mice bearing intracranial human tumor xenografts driven by EGFR amplifications. 达可替尼(Dacomitinib)是人EGFR激酶家族(EGFR/HER1、HER2、HER4)和某些EGFR激活突变(19号外显子缺失或21号外显子L858R突变)的不可逆抑制剂。在体外试验中，达可替尼(Dacomitinib)在临床相关浓度下还可以抑制DDR1、EPHA6、LCK、DDR2和MNK1的活性。在HER家族靶标（包括EGFR突变）驱动的皮下植入的人源肿瘤异种移植小鼠模型中，达可替尼(Dacomitinib)显示出对EGFR和HER2自磷酸化以及肿瘤生长的剂量依赖性抑制作用。达可替尼(Dacomitinib)在由EGFR扩增驱动的人源肿瘤异种颅内移植的口服给药小鼠中也显示出抗肿瘤活性。 FDA-approval:12/2020；NMPA-approval:2019 2023/6/20 sxz D0042
Dasatinib 达沙替尼 Sprycel 施达赛 百时美施贵宝 2006/6/28 FDA/NMPA SPRYCEL is a kinase inhibitor indicated for the treatment of ：1.newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. 2.adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib. 3.adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. 4.pediatric patients 1 year of age and older with Ph+ CML in chronic phase。 5.pediatric patients 1 year of age and older with newly diagnosed Ph+ ALL in combination with chemotherapy. SPRYCEL是一种激酶抑制剂，其适应症为：1.初诊为慢性期费城染色体阳性(Ph+)慢性髓系白血病(CML)成人患者。2.对包括伊马替尼在内的既往治疗中耐药或不耐受的慢性期、加速期、或髓系或淋巴细胞母细胞期Ph+ CML成人患者。3.对既往治疗耐药或不耐受的费城染色体阳性急性淋巴细胞白血病(Ph+ ALL)成人患者。4.慢性期Ph + CML小儿患者(≥1岁)。5.联合化疗用于治疗初诊为Ph+ ALL的小儿患者(≥1岁)。 慢性髓系白血病、急性淋巴细胞白血病 Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase.In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate- sensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under the conditions of the assays, dasatinib could overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression. 达沙替尼(Dasatinib)在纳摩尔浓度水平下可以抑制以下激酶的活性:BCR-ABL、 SRC家族(SRC、LCK、YES、FYN)、c-KIT、EPHA2和PDGFRβ。根据模型研究预计，达沙替尼(Dasatinib)能够与ABL激酶的多种构象结合。在体外研究中，达沙替尼(Dasatinib)在表达各种对甲磺酸伊马替尼(Imatinib mesylate)敏感和耐药疾病的白血病细胞系中也具有活性。达沙替尼(Dasatinib)可以抑制过表达BCR-ABL的慢性髓细胞白血病(CML)和急性淋巴细胞白血病(ALL)细胞系的生长。在非临床试验条件下，达沙替尼(Dasatinib)可以克服由以下原因导致的伊马替尼(Imatinib)耐药：BCR-ABL激酶区突变、SRC家族激酶(LYN、HCK)的替代信号通路激活以及多药耐药性基因过表达。 06/2021 2021/11/26 D0043
Zoligratinib Ch5183284 has been used in trials studying the treatment of Solid Tumours. Zoligratinib (Debio 1347; CH5183284) 是口服可用，选择性的 FGFR 抑制剂，抑制FGFR1，FGFR2和 FGFR3的IC50 值分别为9.3，7.6，22 and 290 nM。 Ch5183284已用于研究治疗固体瘤的试验中。 231008 pj D0044 新增作用机制内容，更新药物名称 LXL
Fam-trastuzumab deruxtecan-nxki 德曲妥珠单抗 Enhertu 优赫得 第一三共 2019-12-20 00:00:00 FDA/NMPA ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of: 1.adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either: in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy. 2.adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. 3.adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.4.adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen. ENHERTU是一种HER2靶向抗体和拓扑异构酶抑制剂偶联物，其适应症为：1.携带HER2阳性，前期已接受过以抗HER2为基础的治疗(转移性疾病治疗或新辅助/辅助治疗）并在完成治疗期间或6个月内出现疾病复发的不可切除性或转移性乳腺癌成人患者。2.患者ERBB2低表达(IHC 1+或IHC 2+/ISH-)且在疾病转移后接受过化疗或在完成辅助化疗期间或6个月内发生疾病复发的不可切除或转移性成年乳腺癌患者。3.携带HER2 (ERBB2)激活突变的不可切除或转移性非小细胞肺癌(NSCLC)成人患者。4.既往接受过基于曲妥珠单抗治疗的HER2阳性、局部进展或转移性胃或胃食管交界处腺癌的成人患者。2023年2月24日，NMPA批准德曲妥珠单抗用于治疗既往接受过一种或一种以上抗人表皮生长因子受体2（HER2）药物治疗的不可切除或转移性HER2阳性成人乳腺癌患者。2023年7月12日，德曲妥珠单抗的新适应证上市申请获得中国国家药品监督管理局（NMPA）批准， 单药适用于治疗既往在转移性疾病阶段接受过至少一种系统治疗的，或在辅助化疗期间或完成辅助化疗之后6个月内复发的，不可切除或转移性HER2低表达（IHC 1+或IHC 2+/ISH-）成人乳腺癌患者。 乳腺癌、胃癌、胃食管交界处腺癌 Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody-drug conjugate. The antibody is a humanized anti-HER2 IgG1. The small molecule, DXd, is a topoisomerase I inhibitor attached to the antibody by a cleavable linker. Following binding to HER2 on tumor cells, fam-trastuzumab deruxtecan-nxki undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death. Fam-trastuzumab deruxtecan-nxki是一种HER2定向抗体药物偶联物。该抗体为人源化抗HER2 IgG1。小分子DXd是一种拓扑异构酶I抑制剂，通过可切割的接头与抗体相连。与肿瘤细胞上的HER2结合后，Fam-trastuzumab deruxtecan-nxki通过溶酶体酶进行内化和细胞内接头裂解。释放后，膜渗透性DXd会导致DNA损伤和细胞凋亡。 05/2022 231107 pj D0045 适应症描述修改，新增NMPA适应症 LXL
Durvalumab 度伐利尤单抗 Imfinzi 英飞凡 阿斯利康 2017/5/1 FDA/NMPA IMFINZI is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: 1. for the treatment of adult patients with unresectable, Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. 2.in combination with etoposide and either carboplatin or cisplatin, as first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). IMFINZI是一种程序性死亡配体1(PD-L1)阻断抗体，其适应症为：1.铂类同步放化疗后疾病未进展的不可切除性III期非小细胞肺癌(NSCLC)成人患者。2.与依托泊苷，卡铂或顺铂联用，用于广泛期小细胞肺癌(ES-SCLC)成人患者的一线治疗。 非小细胞肺癌、小细胞肺癌 Expression of programmed cell death ligand-1 (PD-L1) can be induced by inflammatory signals (e.g., IFN-gamma) and can be expressed on both tumor cells and tumor-associated immune cells in the tumor microenvironment. PD-L1 blocks T-cell function and activation through interaction with PD-1 and CD80 (B7.1). By binding to its receptors, PD-L1 reduces cytotoxic T-cell activity, proliferation, and cytokine production. Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD- L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity (ADCC). PD-L1 blockade with durvalumab led to increased T-cell activation in vitro and decreased tumor size in co-engrafted human tumor and immune cell xenograft mouse models. PD-L1的表达能被炎症信号所诱导（如IFN-gamma）,且能在肿瘤细胞和肿瘤相关的免疫细胞中表达。PD-L1通过和PD-1及B7.1的结合来抑制T细胞的功能及活性。PD-L1和其受体结合将抑制细胞毒性T细胞的活性，抑制T细胞的增殖及细胞因子的产生。Durvalumab是人免疫球蛋白IgG1κ单克隆抗体，Durvalumab和PD-L1结合将阻止PD-L1和PD-1/B7.1结合，从而解除PD-L1在免疫应答（包括抗肿瘤免疫应答）中的抑制作用。通过Durvalumab阻断PD-L1，在体外试验中发现T细胞活性增高，在人肿瘤和免疫细胞共移植小鼠模型中发现肿瘤体积变小。 07/2021 2021/11/26 pj/sjz D0048
Enasidenib 恩西地平 Idhifa 新基制药 2017/8/1 FDA IDHIFA is an isocitrate dehydrogenase-2 inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDAapproved test. IDHIFA是一种异柠檬酸脱氢酶-2抑制剂，适用于携带异柠檬酸脱氢酶-2 (IDH2)突变的复发性或难治性急性髓系白血病(AML)成人患者。 急性髓系白血病 Enasidenib is a selective inhibitor of IDH2, a mitochondria-localized enzyme involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification(PubMed:27721426). Wild-type IDH proteins play a cruicial role in the Krebs/citric acid cycle where it catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate. In comparison, mutant forms of IDH2 enzyme mediates a neomorphic activity and catalyze reduction of α-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked cellular differentiation of hematopoietic progenitor cells(PubMed:27721426). Enasidenib primarily targets the mutant IDH2 variants R140Q, R172S, and R172K with higher potency than the wild type enzyme form. Inhibition of the enzyme leads to decreased levels of 2-hydroxyglutarate (2-HG) and promotion of proper differentiation and clonal proliferation of cells of the myeloid lineage(PubMed:28588020). 恩西地平（Enasidenib）是IDH2的选择性抑制剂，IDH2是一种线粒体酶，参与多种细胞进程，包括缺氧适应、组蛋白去甲基化和DNA修饰（PubMed: 27721426）。野生型IDH蛋白在Krebs/柠檬酸循环中起关键作用，它催化异柠檬酸氧化脱羧成α-酮戊二酸。相比之下，IDH2突变后可产生一种新型酶，催化α-KG还原为2-羟基戊二酸的对映异构体（R），该产物与DNA和组蛋白的超甲基化，基因表达的改变以及造血祖细胞分化的阻断有关（PubMed: 27721426）。恩西地平（Enasidenib）主要靶向IDH2的R140Q，R172S和R172K突变酶，其效力高于野生型酶。对酶的抑制作用可导致2-羟基戊二酸（2-HG）水平降低，并促进骨髓细胞的适当分化和克隆增殖（PubMed: 28588020）。 11/2020 2021/11/26 D0050
Encorafenib 康奈非尼 Braftovi Array BioPharma Inc 2018/6/27 FDA BRAFTOVI is a kinase inhibitor indicated: in combination with binimetinib, 1.for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. 2. in combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy. BRAFTOVI是一种激酶抑制剂，其适应症为：1.联合贝美替尼用于治疗BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。2.联合西妥昔单抗用于BRAF V600E突变的转移性结直肠癌(CRC)成人患者的二线治疗。 黑色素瘤、结直肠癌 Enasidenib is a small molecule inhibitor of the isocitrate dehydrogenase 2 (IDH2) enzyme. Enasidenib targets the mutant IDH2 variants R140Q, R172S, and R172K at approximately 40-fold lower concentrations than the wild-type enzyme in vitro. Inhibition of the mutant IDH2 enzyme by enasidenib led to decreased 2-hydroxyglutarate (2-HG) levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH2 mutated AML. In blood samples from patients with AML with mutated IDH2, enasidenib decreased 2-HG levels, reduced blast counts and increased percentages of mature myeloid cells. 康奈非尼（Enasidenib）是异柠檬酸脱氢酶2（IDH2）酶的小分子抑制剂。 在体外康奈非尼（Enasidenib）靶向结合IDH2突变R140Q、R172S和R172K的能力比野生型酶高约40倍。 康奈非尼（Enasidenib）对IDH2突变酶的抑制导致2-羟基戊二酸（2-HG）水平降低，可在体外试验和IDH2突变AML的小鼠异种移植模型中诱导髓样分化。 在携带IDH2突变AML患者的血液样本中，康奈非尼（Enasidenib）可降低2-HG水平，减少原始细胞（blast）计数，并增加成熟髓样细胞的百分比。 04/2020 2021/11/26 D0051
Entrectinib 恩曲替尼 Rozlytrek 罗圣全 Roche Pharma (Schweiz) AG 2019/8/15 0:00 FDA/NMPA Entrectinib is a kinase inhibitor indicated for the treatment of: 1.Adult patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.2.Adult and pediatric patients 12 years of age and older with solid tumors that: have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion as detected by an FDA-approved test without a known acquired resistance are metastatic or where surgical resection is likely to result in severe morbidity, and mutation, have progressed following treatment or have no satisfactory alternative therapy. 恩曲替尼是一种激酶抑制剂，其适应症为：1.ROS1阳性的转移性非小细胞肺癌(NSCLC)成人患者。2.神经营养性酪氨酸受体激酶(NTRK)基因融合阳性、无已知的获得性耐药突变、转移性或手术切除可能导致严重发病率、且治疗后进展或没有令人满意的替代疗法的成人和儿童(≥12岁)实体瘤患者。2022年NMPA官方公示：恩曲替尼获批上市，用于治疗成人及12岁以上儿童患者神经营养原肌球蛋白受体激酶（NTRK）融合阳性、初始治疗后局部晚期或转移性实体肿瘤。用于治疗ROS1阳性的局部晚期或转移性非小细胞肺癌成人患者。 非小细胞肺癌、实体瘤 Entrectinib is an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1, NTRK2, and NTRK3, respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK) with IC50 values of 0.1 to 2 nM. Entrectinib also inhibits JAK2 and TNK2 with IC50 values > 5 nM. The major active metabolite of entrectinib, M5, showed similar in vitro activity against TRK, ROS1, and ALK.Fusion proteins that include TRK, ROS1, or ALK kinase domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Entrectinib demonstrated in vitro and in vivo inhibition of cancer cell lines derived from multiple tumor types harboring NTRK, ROS1, and ALK fusion genes.Entrectinib demonstrated steady-state brain-to-plasma concentration ratios of 0.4 – 2.2 in multiple animal species (mice, rats, and dogs) and demonstrated in vivo anti-tumor activity in mice with intracranial implantation of TRKA- and ALK-driven tumor cell lines. 恩曲替尼（Entrectinib）是一种靶向原肌球蛋白受体酪氨酸激酶（TRK）TRKA，TRKB和TRKC（分别由神经营养酪氨酸受体激酶[NTRK]基因NTRK1、NTRK2和NTRK3编码），由原癌基因编码的酪氨酸蛋白激酶ROS1（ROS1），以及间变性淋巴瘤激酶（ALK）的抑制剂，其IC50值为0.1至2 nM。恩曲替尼（Entrectinib）还可以抑制JAK2和TNK2的活性，IC50值>5 nM。恩曲替尼（Entrectinib）的主要活性代谢产物M5对TRK、ROS1和ALK的体外活性相似。包含TRK、ROS1或ALK激酶结构域的融合蛋白可以过度激活下游信号传导通路，导致细胞增殖不受限制，凭此驱动致癌潜力。恩曲替尼（Entrectinib）在体外和体内试验中都显示出对携带NTRK、ROS1和ALK融合基因的多种肿瘤类型的癌细胞系具有抑制作用。恩曲替尼（Entrectinib）在多种动物模型（小鼠、大鼠和狗）中的稳态脑血药物浓度比值为0.4-2.2，并且在颅内植入TRKA和ALK驱动肿瘤细胞系的小鼠体内表现出抗肿瘤活性。 07/2022 2023/5/26 0:00 sxz D0054 批准单位更新 LXL
Erdafitinib 厄达替尼 Balversa 杨森生物 2019/4/12 FDA BALVERSA is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has susceptible FGFR3 or FGFR2 genetic alterations and progressed during or following at least one line of prior platinumcontaining chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. BALVERSA是一种激酶抑制剂，适用于既往接受至少一种含铂化疗期间（新辅助或辅助含铂化疗的12个月内）或之后疾病进展的携带FGFR3或FGFR2易感遗传变异的局部晚期或转移性尿路上皮癌成人患者。 尿路上皮癌 Urothelial cancer is statistically the fourth most common kind of cancer in the world. In general, such urothelial cancers originate in the urothelium - or the transitional epithelium - a membrane that covers the renal pelvis to the ureter, the bladder, and the proximal two-thirds of the urethra. While 90 to 95% of urothelial cancers are bladder cancers and the other 5 to 10% are upper tract urothelial cancers, the bladder cancers can also be either superficial or invasive (either not having or having invaded the deeper layers of the bladder).Moreover, fibroblast growth factor receptor (FGFR) is a transmembrane protein that is expressed ubiquitously in normal tissues and is involved in various endogenous bio-physiological processes including the homeostasis of phosphate and vitamin D, cell proliferation, cell anti-apoptotic signaling, and cell migration in a variety of cell types(PubMed:28965185). Concurrently, genetic mutations or changes like deregulation of FGFR pathways and FGFR aberrations such as gene amplification, point mutations, and chromosomal translocations have been implicated in the pathogenesis of urothelial cancer, including the possibility of such changes to all four FGFR genes (FGFR1, FGFR2, FGFR3, and FGFR4)(PubMed:28965185). Changes to the FGFR genes are consequently thought to promote cell proliferation, migration, angiogenesis, and anti-apoptosis in many cancers including urothelial cancer(PubMed:28965185).Erdafitinib is subsequently an oral selective pan-FGFR kinase inhibitor that binds to and inhibits the enzymatic activity of expressed FGFR1, FGFR2, FGFR3, and FGFR4 based on in vitro data(PubMed:28965185,PubMed:26324363). In particular, erdafitinib demonstrates inhibition of FGFR phosphorylation and signaling as well as decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions(PubMed:28965185,PubMed:26324363). Erdafitinib demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer(PubMed:28965185,PubMed:26324363). 统计数据显示，尿路上皮癌已成为全球第四大常见肿瘤。通常而言，尿路上皮癌起源于尿道上皮（或称移行上皮，一种覆盖肾盂至输尿管、膀胱和尿道近端三分之二的膜）。90-95%的尿路上皮癌是膀胱癌，而其他5-10%是上尿路上皮癌，膀胱癌根据是否侵入膀胱深层可分为浅表性或浸润性膀胱癌。此外，成纤维细胞生长因子受体（FGFR）是一种跨膜蛋白，在正常组织中广泛表达，并参与各种内源性生理进程，包括磷酸盐和维生素D稳态，多种细胞类型的增殖、抗凋亡信号和迁移（PubMed: 28965185）。同时，包括FGFR通路失控和FGFR畸变（如基因扩增、点突变和染色体易位）在内的基因突变或遗传变异，都与尿路上皮癌的发病机理有关，这种变异在所有四个FGFR基因（FGFR1、FGFR2、FGFR3和FGFR4）上都有可能发生（PubMed: 28965185）。因此，FGFR基因变异被认为可促进多种肿瘤（包括尿路上皮癌）细胞的增殖、迁移，血管生成和抗凋亡（PubMed: 28965185）。厄达替尼（Erdafitinib）是一种口服选择性泛FGFR激酶抑制剂，基于体外试验数据，该抑制剂与表达的FGFR1、FGFR2、FGFR3和FGFR4结合<E7BB93>
Erlotinib 厄洛替尼 Tarceva 特罗凯 罗氏制药 2004/11/18 FDA/NMPA TARCEVA is a kinase inhibitor indicated for: 1.The treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test receiving first-line, maintenance, or second or greater line treatment after progression following at least one prior chemotherapy regimen. 2.First-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer, in combination with gemcitabine. TARCEVA是一种激酶抑制剂，其适应症为：1.在至少一种化疗方案失败后接受一线、维持第二线或更多线治疗的表皮生长因子受体(EGFR)19号外显子缺失或21号外显子L858R置换突变的转移性非小细胞肺癌(NSCLC)。2.联合吉西他滨用于局部晚期、不可切除性或转移性胰腺癌的一线治疗。2006年厄洛替尼得到NMPA首次批准，2017年NMPA批准厄洛替尼单药适用于表皮生长因子受体（EGFR）基因具有敏感突变的局部晚期或转移性非小细胞肺癌（NSCLC）患者的治疗，包括一线治疗、维持治疗，或既往接受过至少一次化疗进展后的二线及以上治疗。 非小细胞肺癌、胰腺癌 Epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells. In some tumor cells signaling through this receptor plays a role in tumor cell survival and proliferation irrespective of EGFR mutation status. Erlotinib reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor and thereby inhibiting further downstream signaling. Erlotinib binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higher than its affinity for the wild type receptor. Erlotinib inhibition of other tyrosine kinase receptors has not been fully characterized. 表皮生长因子受体（EGFR）在正常细胞和肿瘤细胞表面都有表达。 在一些肿瘤细胞中，通过该受体的信号传导在肿瘤细胞存活和增殖中均起作用，而与EGFR突变状态无关。厄洛替尼（Erlotinib）可逆地抑制EGFR的激酶活性，阻止受体酪氨酸残基的自磷酸化，进而抑制下游信号传导。厄洛替尼（Erlotinib）对19号外显子缺失或21号外显子（L858R）突变EGFR的结合亲和力高于野生型受体。厄洛替尼（Erlotinib）对其他酪氨酸激酶受体的抑制作用尚未完全表征。 FDA-approval:10/2016;NMPA-approval:2017 2023/6/20 sxz D0056 修改日期；220223；sxz
Everolimus 依维莫司 Afinitor 飞尼妥 诺华制药 2009/3/30 FDA/NMPA AFINITOR is a kinase inhibitor indicated for the treatment of: 1.Postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole. 2.Adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. 3.Adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. 4.Adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.5.AFINITOR and AFINITOR DISPERZ are kinase inhibitors indicated for the treatment of adult and pediatric patients aged 1 year and older with TSC who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.6.AFINITOR DISPERZ is a kinase inhibitor indicated for the adjunctive treatment of adult and pediatric patients aged 2 years and older with TSC-associated partial-onset seizures. AFINITOR是一种激酶抑制剂，其适应症为：1.联合依西美坦用于治疗来曲唑或阿那曲唑治疗失败的绝经后妇女激素受体阳性、HER2阴性的晚期乳腺癌。2.进展性胰腺神经内分泌瘤(PNET)以及不可切除性、局部晚期或转移性的进展性、分化良好的非功能性胃肠道(GI)和肺部神经内分泌瘤(NET)成人患者。3.舒尼替尼或索拉非尼治疗失败的晚期肾细胞癌(RCC)成人患者。4.不需要立即手术的肾血管平滑肌脂肪瘤伴结节性硬化症(TSC)成人患者。5.AFINITOR和AFINITOR DISPERZ作为激酶抑制剂，适用于伴有室管膜下巨细胞星形细胞瘤(SEGA)、需要治疗干预但不可手术切除的TSC成人和儿童(≥1岁)患者。6.AFINITOR DISPERZ是一种激酶抑制剂，用于辅助治疗TSC相关癫痫部分性发作的成人和儿童(≥2岁)患者。2013年依维莫司首次获得NMPA批准，2018年NMPA批准依维莫司适用于治疗以下患者：晚期肾细胞癌成人患者，胰腺神经内分泌瘤成人患者.胃肠道或肺源神经内分泌肿瘤（NET）成人患者，室管膜下巨细胞星形细胞瘤(SEGA)，肾血管平滑肌脂肪瘤伴结节性硬化症。2022年NMPA批准依维莫司用于治疗乳腺癌。 乳腺癌、神经内分泌瘤、肾癌、结节性硬化症、巨细胞星形细胞瘤 Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers and in tuberous sclerosis complex (TSC). Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex 1 (mTORC1) and thus inhibition of mTOR kinase activity. Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic initiation factor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis. S6K1 is a substrate of mTORC1 and phosphorylates the activation domain 1 of the estrogen receptor which results in ligand-independent activation of the receptor. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) and reduced the expression of vascular endothelial growth factor (VEGF).Inhibition of mTOR by everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies.Constitutive activation of the PI3K/Akt/mTOR pathway can contribute to endocrine resistance in breast cancer. In vitro studies show that estrogen-dependent and HER2+ breast cancer cells are sensitive to the inhibitory effects of everolimus, and that combination treatment with everolimus and Akt, HER2, or aromatase inhibitors enhances the anti-tumor activity of everolimus in a synergistic manner.Two regulators of mTORC1 signaling
Fedratinib Inrebic 英派药业 2019/8/16 FDA INREBIC is a kinase inhibitor indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF). INREBIC是一种激酶抑制剂，适用于治疗中危2型或高危原发性或继发性(真性红细胞增多症或原发性血小板增多症后)骨髓纤维化(MF)成人患者。 骨髓纤维化 Fedratinib is an inhibitor of Janus Activated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3(PubMed:26181658).JAK2 is highly active in myeloproliferative neoplasms like myelofibrosis.Fedratinib's inhibition of JAK2 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and 5, which prevents cell division and induces apoptosis(PubMed:24165976). Fedratinib是Janus激酶2(JAK2)和FMS样酪氨酸激酶3的抑制剂(PubMed：26181658)。JAK2在诸如骨髓纤维化的骨髓增殖性肿瘤中高度激活。Fedratinib对JAK2的抑制作用会抑制信号转导子和转录激活子(STAT)3和5的磷酸化，阻止细胞分裂并诱导凋亡(PubMed：24165976)。 08/2019 2021/11/26 D0058
Fruquintinib 呋喹替尼 Fruzaqla 爱优特 和记黄埔 2018-09-04 00:00:00 FDA/NMPA FRUZAQLA is a kinase inhibitor indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. 呋喹替尼是具有高度选择性的肿瘤血管生成抑制剂，适用于既往接受过氟尿嘧啶类、奥沙利铂和伊立替康为基础的化疗，以及既往接受过或不适合接受抗血管内皮生长因子(VEGF)治疗、抗表皮生长因子受体(EGFR)治疗(RAS野生型)的转移性结直肠癌(mCRC)患者。2023年11月8日，Fruzaqla（呋喹替尼）获FDA批准上市，用于治疗既往接受过氟尿嘧啶类、奥沙利铂和伊立替康为基础的化疗，抗VEGF治疗，以及抗EGFR治疗（若属RAS野生型且医学上适用）的成人转移性结直肠癌患者。 结直肠癌 Fruquintinib is a small molecule kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 with IC50 values of 33, 35, and 0.5 nM, respectively. In vitro studies showed fruquintinib inhibited VEGF-mediated endothelial cell proliferation and tubular formation. In vitro and in vivo studies showed fruquintinib inhibited VEGF-induced VEGFR-2 phosphorylation. In vivo studies showed fruquintinib inhibited tumor growth in a tumor xenograft mouse model of colon cancer. 呋喹替尼是一具有高度选择性的肿瘤血管生成抑制剂，其主要作用靶点是VEGFR激酶家族VEGFR1， 2及3。呋喹替尼在分子水平可抑制VEGFR激酶的活性；在细胞水平上可抑制VEGFR2/3的磷酸化，抑制内皮细胞的增殖及管腔形成；在组织水平上，呋喹替尼可明显抑制鸡胚绒毛尿囊膜模型新生微血管的形成；在整体动物水平上，呋喹替尼口服后可抑制VEGFR2/3磷酸化，抑制肿瘤血管生成，从而抑制肿瘤生长。在整体动物上，呋喹替尼采用一日一次给药，对结直肠癌以及其它多种类型肿瘤模型的生长均显示强效且剂量依赖性的抑制效应，在敏感模型上发现肿瘤缩小和消退。 NMPA核准日期:2018年9月4日；FDA-Revised:11/2023 2023-11-10 00:00:00 pj D0059 新增FDA批准信息
Fulvestrant 氟维司群 Faslodex 芙仕得 阿斯利康 2002/4/25 FDA/NMPA FASLODEX is an estrogen receptor antagonist indicated for the treatment of: 1.Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy.2.HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy.3.HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib, as initial endocrine based therapy or following disease progression on endocrine therapy.4.HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. FASLODEX是一种雌激素受体拮抗剂，其适应症包括：1.既往未接受过内分泌治疗的绝经后妇女激素受体(HR)阳性、人表皮生长因子受体2 (HER2)阴性晚期乳腺癌。2.内分泌治疗后疾病进展的绝经后妇女HR阳性晚期乳腺癌。3.联合Ribociclib用于HR阳性、HER2阴性的绝经后妇女晚期或转移性乳腺癌的初始内分泌治疗或内分泌治疗后疾病进展的后续治疗。4.联合哌柏西利或阿贝西利用于治疗内分泌治疗后疾病进展的HR阳性、HER2阴性的晚期或转移性乳腺癌。2010年氟维司群首次获得NMPA批准，2016年NMPA批准氟维司群可用于在抗雌激素辅助治疗后或治疗过程中复发的，或是在抗雌激素治疗中进展的绝经后(包括自然绝经和人工绝经)雌激素受体阳性的局部晚期或转移性乳腺癌。2022年NMPA批准氟维司群联合阿贝西利用于治疗HR阳性、HER2阴性的局部晚期或转移性乳腺癌用于既往接受内分泌治疗后疾病进展的患者。 乳腺癌 Many breast cancers have estrogen receptors (ER) and the growth of these tumors can be stimulated by estrogen. Fulvestrant is an estrogen receptor antagonist that binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol and downregulates the ER protein in human breast cancer cells.In vitro studies demonstrated that fulvestrant is a reversible inhibitor of the growth of tamoxifen-resistant, as well as estrogen-sensitive human breast cancer (MCF-7) cell lines. In in vivo tumor studies, fulvestrant delayed the establishment of tumors from xenografts of human breast cancer MCF-7 cells in nude mice. Fulvestrant inhibited the growth of established MCF-7 xenografts and of tamoxifen-resistant breast tumor xenografts.Fulvestrant showed no agonist-type effects in in vivo uterotrophic assays in immature or ovariectomized mice and rats. In in vivo studies in immature rats and ovariectomized monkeys, fulvestrant blocked the uterotrophic action of estradiol. In postmenopausal women, the absence of changes in plasma concentrations of FSH and LH in response to fulvestrant treatment (250 mg monthly) suggests no peripheral steroidal effects. 许多乳腺癌都有雌激素受体（ER），雌激素可刺激这些肿瘤的生长。氟维司群（Fulvestrant）是一种雌激素受体拮抗剂，可竞争性结合雌激素受体，亲和力与雌二醇相当，并下调人乳腺癌细胞中ER蛋白水平。体外研究表明，氟维司群（Fulvestrant）是他莫昔芬（Tamoxifen）耐药和雌激素敏感的人乳腺癌细胞系（MCF-7）生长的可逆抑制剂。在体内肿瘤研究中，氟维司群（Fulvestrant）可延缓裸鼠体内人乳腺癌MCF-7细胞异种移植物的植入。氟维司群（Fulvestrant）可抑制已植入的MCF-7异种移植物以及他莫昔芬耐药的乳腺肿瘤异种移植物的生长。在未成熟或切除卵巢的小鼠和大鼠的体内子宫增重试验中，氟维司群（Fulvestrant）没有显示出激动剂样作用。在未成熟大鼠和卵巢切除猴的体内研究中，氟维司群（Fulvestrant）可阻断雌二醇的子宫营养作用。绝经后妇女绐予氟维司群（Fulvestrant）250 mg/月
Futibatinib Lytgobi Taiho Oncology Inc 2022/9/30 FDA LYTGOBI is a kinase inhibitor indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2(FGFR2) gene fusions or other rearrangements LYTGOBI是一种激酶抑制剂，适用于治疗携带成纤维细胞生长因子受体2 (FGFR2)基因融合或其他重排的既往治疗过的、不可切除的、局部晚期或转移性肝内胆管癌患者。 肝内胆管癌 Futibatinib is a small molecule kinase inhibitor of FGFR 1, 2, 3, and 4 with IC50 values of less than 4 nM. Futibatinib covalently binds FGFR. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Futibatinib inhibited FGFR phosphorylation and downstream signaling and decreased cell viability in cancer cell lines with FGFR alterations including FGFR fusions/rearrangements, amplifications, and mutations. Futibatinib demonstrated anti-tumor activity in mouse and rat xenograft models of human tumors with activating FGFR genetic alterations Futibatinib是FGFR 1、2、3和4的小分子激酶抑制剂，IC50值小于4 nM。Futibatinib共价结合FGFR。本构FGFR信号可以支持恶性细胞的增殖和存活。Futibatinib抑制FGFR磷酸化和下游信号转导，降低FGFR突变的癌细胞株的细胞活力，包括FGFR融合/重排、扩增和突变。Futibatinib在携带FGFR激活突变的小鼠和大鼠人类肿瘤移植模型中显示了抗肿瘤活性。 09/2022 2022/10/11 sxz D0062 适应症修改
Ipatasertib 罗氏 前列腺癌 Ipatasertib has been used in trials studying the treatment of Cancer, Neoplasms, Solid Cancers, Breast Cancer, and Gastric Cancer, among others. Ipatasertib (GDC-0068) 是一种口服有效的、高选择性和 ATP 竞争性泛 Akt 抑制剂，其对 Akt1/2/3 的 IC50 值分别为 5、18、8 nM。Ipatasertib 通过抑制 Akt 导致非 p53 依赖性的 PUMA 激活，从而同步激活 FoxO3a 和 NF-κB 。Ipatasertib 还能诱导癌细胞凋亡 (apoptosis)，抑制异种移植小鼠模型中的肿瘤生长。 Ipatasertib是罗氏旗下基因泰克与Array BioPharma（已于2019年7月30日被辉瑞收购）共同开发的一款口服的、高度特异性的研究药物，旨在靶向并结合AKT的所有三种亚型，阻断PI3K/AKT信号通路，这是前列腺癌中癌细胞生长和增殖的关键驱动因素。PI3K/AKT通路也与抗雄激素疗法的治疗抵抗有关，因为雄激素受体（AR）抑制与AKT通路激活的增加相关。Ipatasertib治疗转移性去势抵抗性前列腺癌（mCRPC）患者的III期IPATential150研究数据显示：在携带PTEN抑癌基因缺失的患者中，ipatasertib与阿比特龙和泼尼松或泼尼松龙联用，与活性对照相比，显著提高患者的放射学无进展生存期（rPFS）。 231008 pj D0063 修订药物名称，作用机制内容 LXL
Inavolisib 罗氏 实体瘤、乳腺癌 GDC-0077 is under investigation in clinical trial NCT03006172 (To Evaluate the Safety, Tolerability, and Pharmacokinetics of GDC-0077 Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer). Inavolisib (GDC-0077; RG6114) 是一种有效的，口服的选择性 PI3Kα 抑制剂 (IC50=0.038 nM)。GDC-0077 (RG6114) 通过与 PI3K 的 ATP 结合位点结合而发挥其活性，从而抑制了 PIP2 到 PIP3 的磷酸化。与野生型 PI3Kα 相比，GDC-0077 (RG6114) 对突变体的选择性更高。 Inavolisib（RG6114，GDC-0077）是一款靶向PI3Kα突变体的选择性抑制剂。研究显示，inavolisib具有双重作用机制：它不但可以阻断PI3Kα的活性，而且可以促进PI3Kα突变体p110α催化亚基的降解。目前，罗氏正在开展一项国际多中心（含中国）3期临床，以评估inavolisib联合哌柏西利（CDK4/6抑制剂）和氟维司群治疗携带PIK3CA突变的激素受体（HR）阳性、HER2阴性局部晚期或转移性乳腺癌患者的疗效和安全性。 231008 pj D0064 新增作用机制内容 LXL
Apitolisib Apitolisib has been used in trials studying the treatment of Solid Cancers, Breast Cancer, Prostate Cancer, Renal Cell Carcinoma, and Endometrial Carcinoma, among others. Apitolisib (GDC-0980; GNE 390; RG 7422) 是一种口服有效的 PI3K 和 mTOR (TORC1/2) 激酶抑制剂，抑制 PI3Kα/PI3Kβ/PI3Kδ/PI3Kγ 的活性，IC50 值为 5 nM/27 nM/7 nM/14 nM。 抑制mTOR，Ki 为 17 nM。 Apitolisib已用于研究实体癌、乳腺癌、前列腺癌、肾细胞癌和子宫内膜癌等治疗的试验中。 231008 pj D0065 新增作用机制内容 LXL
Gefitinib 吉非替尼 Iressa 易瑞沙 阿斯利康 2015/7/13 FDA/NMPA IRESSA is a tyrosine kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. IRESSA是一种酪氨酸激酶抑制剂，适用于表皮生长因子受体(EGFR)19号外显子缺失或21号外显子置换突变的转移性非小细胞肺癌(NSCLC)。2006年吉非替尼首次获得NMPA批准，至2016年NMPA批准吉非替尼的适应证为单药适用于表皮生长因子受体（EGFR)具有敏感突变的局部晚期或转移性非小细胞肺癌患者的一线治疗。 非小细胞肺癌 The epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells and plays a role in the processes of cell growth and proliferation. Some EGFR activating mutations (exon 19 deletion or exon 21 point mutation L858R) within NSCLC cells have been identified as contributing to the promotion of tumor cell growth, blocking of apoptosis, increasing the production of angiogenic factors and facilitating the processes of metastasis.Gefitinib reversibly inhibits the kinase activity of wild-type and certain activating mutations of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signaling and blocking EGFR-dependent proliferation.Gefitinib binding affinity for EGFR exon 19 deletion or exon 21 point mutation L858R mutations is higher than its affinity for the wild-type EGFR. Gefitinib also inhibits IGF and PDGF-mediated signaling at clinically relevant concentrations; inhibition of other tyrosine kinase receptors has not been fully characterized. 表皮生长因子受体（EGFR）在正常细胞和肿瘤细胞表面都有表达，并在细胞生长和增殖过程中发挥作用。NSCLC细胞中的一些EGFR激活突变（19号外显子缺失或21号外显子L858R点突变）已被确认有助于促进肿瘤细胞生长、阻断凋亡、增加血管生成因子的产生以及促进肿瘤转移。吉非替尼（Gefitinib）可逆地抑制野生型和某些EGFR激活突变的激酶活性，阻止与受体相关的酪氨酸残基的自磷酸化，进而抑制下游信号传导并阻断EGFR依赖性增殖。吉非替尼（Gefitinib）对19号外显子缺失或21号外显子L858R点突变的结合亲和力要高于其对野生型EGFR的亲和力。吉非替尼（Gefitinib）还可以在临床相关浓度下抑制IGF和PDGF介导的信号传导。其他酪氨酸激酶受体的抑制作用尚未完全表征。 FDA-approval:05/2021;NMPA-approval:2022 2023/6/20 sxz D0066
Gilteritinib 吉瑞替尼 Xospata 适加坦 安斯泰来 2018/11/28 FDA/NMPA XOSPATA is a kinase inhibitor indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. XOSPATA是一种激酶抑制剂，适用于携带FLT3突变的复发性或难治性急性髓系白血病(AML)成人患者。 急性髓系白血病 Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD. 吉列替尼（Gilteritinib）是一种小分子抑制剂，可抑制多种受体酪氨酸激酶的活性，包括FMS样酪氨酸激酶3（FLT3）。吉列替尼（Gilteritinib）在外源性表达FLT3的细胞（包括FLT3-ITD、酪氨酸激酶域突变（TKD）FLT3-D835Y和FLT3-ITD-D835Y）中表现出抑制FLT3受体信号转导和细胞增殖的能力，还可以诱导表达FLT3-ITD的白血病细胞凋亡。 05/2019 2021/11/26 D0067
GSK2636771 GSK2636771 has been used in trials studying the treatment of CANCER, LYMPHOMA, Solid Neoplasm, Recurrent Solid Neoplasm, and Advanced Malignant Neoplasm, among others. GSK2636771是一种口服生物有效的PI3Kβ选择性抑制剂，其对PI3Kβ的选择性比对PI3Kα/PI3Kγ高900倍以上，比对PI3Kδ的选择性大10倍以上。对PTEN缺失细胞系敏感。 GSK2636771已用于癌症、淋巴瘤、实体瘤、复发性实体瘤和晚期恶性肿瘤等治疗的研究试验中。 230919 pj D0068 新增作用机制内容 LXL
H3B-8800 H3B-8800 is thought to bind to a site similar to pladienolides on the SF3B complex within the spliceosome(PubMed:29457796). Once bound it induces increased retention of short (<300 nucleotide) GC-rich introns through modulation of pre-mRNA processing. These intron-retained mRNA sequences are then thought to be destroyed through the nonsense-mediated decay pathway. It has been suggested that modulation by H3B-8800 is mediated by disruption of branchpoint sequence recognition by the SF3B complex as there is overall less preference for adenosine as the branchpoint nucleotide and a greater amount of sequences with weaker association to the SFB3 in introns retained with H3B-8800.It was found that 41 of 404 genes encoding spliceosome proteins contained GC-rich sequences whose retention was induced by H3B-8800(PubMed:29457796). It is suggested that this is key to the specificity of H3B-8800's lethality as cells with spliceosome-mutant cells are dependent on the expression of wild-type spliceosome components for survival(PubMed:27776121). Since cancer cells, as in myelodysplasia, experience SF3B1 mutations much more frequently than host cells, this allows H3B-8800 to be used to preferentially target these cells by inducing intron-retention in critical spliceosome component pre-mRNA leading to destruction of the now nonsense mature RNA ultimately cell-death due to the lack of these critical proteins(PubMed:29457796,PubMed:21909114). 目前认为H3B-8800与剪接体中和SF3B复合物上的普拉二烯内酯相似的位点相结合（PubMed: 29457796）。结合后可通过调控pre-mRNA加工，诱导增加短（<300个核苷酸）且富含GC序列的内含子保留。这些内含子保留的mRNA序列通过无义介导的mRNA衰变途径被降解。有人提出，H3B-8800的调控机制是通过破坏SF3B复合物对分支点序列的识别来介导的，因为在H3B-8800保留的内含子中，总体而言腺苷作为分支点核苷酸的偏好较小，而与SFB3关联性较弱的序列则较多。目前在404个编码剪接体蛋白的基因中已发现有41个具有富含GC的序列，可被H3B-8800诱导内含子保留（PubMed: 29457796）。这是H3B-8800特异性致死的关键，因为剪接体突变细胞的存活依赖于野生型剪接体成分的表达（PubMed: 27776121）。由于肿瘤细胞（如骨髓增生异常）比宿主细胞发生SF3B1突变的频率要高得多，这使得H3B-8800可优先靶向这些细胞，诱导关键剪接体成分pre-mRNA的内含子保留，导致无义的成熟RNA降解，最终导致细胞由于缺少这些关键蛋白而死亡（PubMed: 29457796，PubMed: 21909114）。 2021/11/26 D0069
Ibrutinib 伊布替尼 Imbruvica 亿珂 Pharmacyclics LLC 2013/11/13 FDA/NMPA IMBRUVICA is a kinase inhibitor indicated for the treatment of: Adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. 2.Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL). 3.Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion.4.Adult patients with Waldenstrm’s macroglobulinemia (WM).5. Adult patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy. 6.Adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy. 伊布替尼是一种激酶抑制剂，其适应症包括：1.既往至少接受过一次治疗的套细胞淋巴瘤(MCL)成人患者。2.慢性淋巴细胞白血病(CLL)/小淋巴细胞淋巴瘤(SLL)成人患者。3.伴17p缺失的慢性淋巴细胞白血病(CLL)/小淋巴细胞淋巴瘤(SLL)成人患者。4.华氏巨球蛋白血症(WM)成人患者。5.需要全身治疗并且至少接受过一次抗CD20为基础治疗的边缘区淋巴瘤(MZL)成人患者。6.既往接受一线或多线系统治疗失败后的慢性移植物抗宿主病(cGVHD)成人和儿童（≥1岁）患者。 套细胞淋巴瘤、慢性淋巴细胞白血病/小淋巴细胞淋巴瘤、华氏巨球蛋白血症、慢性移植物抗宿主病 Ibrutinib is a small-molecule inhibitor of BTK. Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. BTK’s role in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion. Nonclinical studies show that ibrutinib inhibits malignant B-cell proliferation and survival in vivo as well as cell migration and substrate adhesion in vitro. 伊布替尼（Ibrutinib）是BTK的小分子抑制剂。伊布替尼（Ibrutinib）与BTK活性位点中的半胱氨酸残基形成共价键，从而抑制BTK酶活性。BTK是B细胞抗原受体（BCR）和细胞因子受体途径的信号传导分子。BTK在B细胞表面受体信号转导中的作用可导致B细胞运输、趋化性和粘附所必需的通路激活。非临床研究表明，伊布替尼（Ibrutinib）在体内可抑制恶性B细胞增殖和存活，以及在体外可抑制细胞迁移和底物粘附。 08/2022 2022/9/9 sxz D0070 适应症修改
Imatinib 伊马替尼 Glivec 格列卫 诺华制药 2001/5/10 FDA/NMPA Gleevec is a kinase inhibitor indicated for the treatment of: 1.Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase . 2.Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy. 3.Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). 4.Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy . 5.Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements . 6.Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown. 7. Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. 8.Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP). 9.Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). 10.Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST. Gleevec是一种激酶抑制剂，其适应症为：1.初诊为费城染色体阳性慢性髓系白血病(Ph+ CML)慢性期成人和儿童患者。2.干扰素治疗失败的费城染色体阳性慢性髓系白血病(Ph+ CML)急变期(BC)、加速期(AP)或慢性期(CP)患者。3.复发性或难治性费城染色体阳性急性淋巴细胞白血病(Ph+ ALL)成人患者。4.联合化疗用于治疗初诊为费城染色体阳性急性淋巴细胞白血病(Ph+ ALL)儿童患者。5.伴有血小板衍生生长因子受体(PDGFR)基因重排的骨髓增生异常综合症/骨髓增殖性疾病(MDS/MPD)成人患者。6.无D816V c-Kit突变或c-Kit突变状态未知的侵袭性系统性肥大细胞增生症(ASM)成人患者。7.具有FIP1L1-PDGFRα融合激酶(CHIC2等位基因缺失的突变分析或FISH显示)的高嗜酸性粒细胞综合征(HES)和/或慢性嗜酸性粒细胞白血病(CEL)成人患者，以及FIP1L1-PDGFRα融合激酶阴性或未知的HES和/或CEL患者。8.不可切除性、复发性和/或转移性隆突性皮肤纤维肉瘤(DFSP)成人患者。9.Kit(CD117)阳性的不可切除性和/或转移性恶性胃肠道间质瘤(GIST)。10.Kit(CD117)阳性GIST的切除术后辅助化疗。 慢性髓系白血病、急性淋巴细胞白血病、骨髓增生异常综合症/骨髓增殖性疾病、侵袭性系统性肥大细胞增生症、高嗜酸性粒细胞综合征/慢性嗜酸性粒细胞白血病、隆突性皮肤纤维肉瘤、胃肠道间质瘤 Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Imatinib inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia. Imatinib inhibits colony formation in assays using ex vivo peripheral blood and bone marrow samples from CML patients.In vivo, imatinib inhibits tumor growth of BCR-ABL transfected murine myeloid cells as well as BCR-ABL positive leukemia lines derived from CML patients in blast crisis.Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces apoptosis in GIST cells, which express an activa
Ivosidenib 艾伏尼布 Tibsovo 施维雅 2018/7/20 FDA TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible IDH1 mutation as detected by an FDA-approved test with：1.Newly Diagnosed Acute Myeloid Leukemia (AML)In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy 2.Relapsed or refractory AML. For the treatment of adult patients with relapsed or refractory AML. 3.Locally advanced or metastatic cholangiocarcinoma For the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma who have been previously treated. TIBSOVO是一种异柠檬酸脱氢酶-1 (IDH1)抑制剂用于易感IDH1突变的患者，其适应症为：1.急性髓系白血病(AML)：(1)与azacitidine联合使用或作为单药用于新诊断的年龄≥75岁或者因合并症无法使用强化诱导化疗的成人患者. 2.复发性或难治性AML成人患者。3.局部晚期或转移性胆管癌：既往接受过治疗的局部晚期或转移性的胆管癌患者。 急性髓系白血病、胆管癌 Ivosidenib is a small molecule inhibitor that targets the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of ivosidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of ivosidenib sustainable at the recommended dosage according to validated methods. The most common of such mutations are R132H and R132C substitutions.Ivosidenib was shown to inhibit selected IDH1 R132 mutants at much lower concentrations than wild-type IDH1 in vitro. Inhibition of the mutant IDH1 enzyme by ivosidenib led to decreased 2- HG levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH1-mutated AML. In blood samples from patients with AML with mutated IDH1, ivosidenib decreased 2-HG levels ex-vivo, reduced blast counts, and increased percentages of mature myeloid cells. Ivosidenib是靶向异柠檬酸脱氢酶1（IDH1）酶突变的小分子抑制剂。IDH1易感突变定义为可导致白血病细胞中2-羟基戊二酸（2-HG）水平升高的突变，其功效可通过以下方法预测：1）依维西尼布推荐剂量下具有临床意义的缓解，和/或2）根据验证方案，在推荐剂量可持续浓度下的依维替尼对IDH1突变酶活性的抑制作用。最常见的此类突变是R132H和R132C替换。Ivosidenib在体外能以比抑制野生型IDH1低得多的浓度选择性抑制IDH1 R132突变。Ivosidenib对突变IDH1酶的抑制在体外试验和IDH1突变AML小鼠异种移植模型中可导致2-HG水平降低，并诱导髓样分化。在IDH1突变AML患者的血液样本中，Ivosidenib可降低离体的2-HG水平，减少原始细胞计数，并增加成熟髓样细胞的百分比。 05/2022 2022/6/6 sxz D0074
Lapatinib 拉帕替尼 Tykerb 泰立沙 诺华制药 2007/7/13 FDA/NMPA TYKERB is a kinase inhibitor indicated in combination with:1.capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress human epidermal growth factor receptor 2 (HER2) and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. 2.letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated. TYKERB是一种激酶抑制剂，其适应症为：1.联合卡培他滨用于治疗过表达人表皮生长因子受体2(HER2)并且既往接受过蒽环类、紫杉类和曲妥珠单抗等治疗的晚期或转移性乳腺癌。2.联合来曲唑用于治疗过表达HER2受体适用激素治疗的绝经后妇女激素受体阳性转移性乳腺癌。2013年拉帕替尼片首次获得NMPA批准，至2018年NMPA批准拉帕替尼与卡培他滨联用适用于HER2过度表达且既往接受过包括蒽环类,紫杉类和曲妥珠单抗治疗的晚期或转移性乳腺癌患者的治疗。 乳腺癌 Lapatinib is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and of Human Epidermal Receptor Type 2 (HER2 [ErbB2]) receptors (estimated Kiapp values of 3nM and 13nM, respectively) with a dissociation half-life of greater than or equal to 300 minutes. Lapatinib inhibits ErbB-driven tumor cell growth in vitro and in various animal models.An additive effect was demonstrated in an in vitro study when lapatinib and 5-FU (the active metabolite of capecitabine) were used in combination in the 4 tumor cell lines tested. The growth inhibitory effects of lapatinib were evaluated in trastuzumab-conditioned cell lines. Lapatinib retained significant activity against breast cancer cell lines selected for long-term growth in trastuzumab-containing medium in vitro. These in vitro findings suggest non-cross-resistance between these two agents.Hormone receptor-positive breast cancer cells (with ER [Estrogen Receptor] and/or PgR [Progesterone Receptor]) that coexpress the HER2 tend to be resistant to established endocrine therapies. Similarly, hormone receptor-positive breast cancer cells that initially lack EGFR or HER2 upregulate these receptor proteins as the tumor becomes resistant to endocrine therapy. 拉帕替尼（Lapatinib）是一种4-苯胺喹唑啉类抑制剂，可抑制人表皮生长因子受体（EGFR [ErbB1]）和人表皮生长因子受体2（HER2 [ErbB2]）的胞内酪氨酸激酶结构域活性（预估Kiapp值分别为3 nM和13 nM），消除半衰期大于或等于300分钟。拉帕替尼（Lapatinib）可在体外和各种动物模型中抑制ErbB驱动的肿瘤细胞生长。在一项体外研究的4种受试肿瘤细胞系中，拉帕替尼（Lapatinib）和 5-FU（卡培他滨的活性代谢物）联合用药显示出相加作用。在对曲妥珠单抗（Trastuzumab）耐受的细胞系中拉帕替尼（Lapatinib）的生长抑制作用已得到评估。拉帕替尼（Lapatinib）对于可在含曲妥珠单抗（Trastuzumab）培养基中长期生长的乳腺癌细胞系也保持显著活性。这些体外研究表明，这两种药物之间没有交叉耐药性。共表达HER2的激素受体阳性乳腺癌细胞（如雌激素受体[ER]和/或孕激素受体[PgR]）易对内分泌治疗产生耐受。同样，激素受体阳性乳腺癌细胞缺乏EGFR或HER2时会上调这些受体蛋白表达，使肿瘤对内分泌治疗耐受。 FDA-approval:12/2018;NMPA-approval:2022 2023/6/20 sxz D0075
Larotrectinib 拉罗替尼 Vitrakvi 拜耳医药 2018/11/26 FDA/NMPA VITRAKVI is a kinase inhibitor indicated for the treatment of adult and pediatric patients with solid tumors that: 1.have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation,.are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. VITRAKVI是一种激酶抑制剂，适用于神经营养性酪氨酸受体激酶(NTRK)基因融合阳性、无已知的获得性耐药突变、转移性或手术切除可能导致严重发病率、且没有令人满意的替代疗法或治疗后进展的成人和儿童实体瘤患者。2022年NMPA批准洛拉替尼单药适用于间变性淋巴瘤激酶（ALK）阳性的局部晚期或转移性非小细胞肺癌患者的治疗。 实体瘤 Larotrectinib is an inhibitor of the tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC. In a broad panel of purified enzyme assays, larotrectinib inhibited TRKA, TRKB, and TRKC with IC50 values between 5-11 nM. One other kinase TNK2 was inhibited at approximately 100-fold higher concentration. TRKA, B, and C are encoded by the genes NTRK1, NTRK2, and NTRK3.Chromosomal rearrangements involving in-frame fusions of these genes with various partners can result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines.In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression. Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R. Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L. 拉罗替尼（Larotrectinib）是原肌球蛋白受体激酶（TRK）A/B/C抑制剂。在一项广泛的纯化酶检测中，拉罗替尼（Larotrectinib）抑制TRKA，TRKB和TRKC，IC50值为5-11 nM。另一种激酶TNK2在大约100倍的浓度下被抑制。TRKA/B/C分别由NTRK1/2/3基因编码。这些基因与各种伴侣基因框内融合导致的染色体重排可以产生组成性激活的嵌合TRK融合蛋白，其可以作为致癌驱动剂，促进肿瘤细胞系的细胞增殖和存活。在体外试验和体内肿瘤模型中，拉罗替尼（Larotrectinib）在由基因融合、蛋白调节结构域缺失或细胞过表达TRK蛋白所产生的TRK蛋白组成性激活细胞中显示出抗肿瘤活性。拉罗替尼（Larotrectinib）在TRKA激酶结构域中发生点突变的细胞系中具有最小的活性，包括临床鉴定的获得性抗性突变G595R。临床已鉴定的TRKC激酶结构域中的拉罗替尼（Larotrectinib）获得性抗性点突变包括G623R、G696A和F617L。 FDA-approval:03/2021 2023/6/20 sxz D0076 添加NMPA的批准单位.20220415.sxz
Lenvatinib 仑伐替尼 Lenvima 乐卫玛 卫材药业 2015/2/13 FDA/NMPA LENVIMA is a kinase inhibitor that is indicated: 1.Differentiated Thyroid Cancer (DTC) :For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC).2.Renal Cell Carcinoma (RCC):(1)In combination with pembrolizumab, for the first line treatment of adult patients with advanced renal cell carcinoma (RCC). （2）In combination with everolimus, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy. 3.Hepatocellular Carcinoma (HCC):For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). 4.Endometrial Carcinoma (EC):In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma (EC) that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. LENVIMA是一种激酶抑制剂，其适应症包括：1.局部复发或转移性、进展性、放射性碘难治性分化型甲状腺癌(DTC)。2.联合Pembrolizumab用于晚期肾细胞癌成人患者的一线治疗，或联合依维莫司用于治疗既往接受过抗血管生成药物治疗的晚期肾细胞癌(RCC)成人患者。3.不可切除性肝细胞癌(HCC)的一线治疗。4.联合帕博利珠单抗用于治疗正常错配修复或非微卫星高不稳定性(MSI-H)的在既往接受系统治疗后病情进展、且不适合根治性手术或放射治疗的晚期子宫内膜癌(EC)。 甲状腺癌、肾细胞癌、肝细胞癌、子宫内膜癌 Lenvatinib is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2α (FRS2α) phosphorylation.In syngeneic mouse tumor models, lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.The combination of lenvatinib and everolimus showed increased antiangiogenic and antitumor activity as demonstrated by decreases in human endothelial cell proliferation, tube formation, and VEGF signaling in vitro, and by decreases in tumor volume in mouse xenograft models of human renal cell cancer that were greater than those with either drug alone. 仑伐替尼(Lenvatinib)是一种受体酪氨酸激酶(RTK)抑制剂，抑制血管内皮生长因子的激酶活性(VEGF)的受体VEGFR1(FLT1)，VEGFR2(KDR)，和VEGFR3(FLT4)。仑伐替尼(Lenvatinib)还能抑制除正常细胞功能外与致病性血管生成、肿瘤生长以及癌症进展相关的其它激酶，包括成纤维细胞生长因子(FGF)受体FGFR1、2、3和4；血小板衍生生长因子受体α(PDGFRα)、KIT和RET。仑伐替尼(Lenvatinib)在肝细胞癌细胞系中还表现出抗增殖活性,这取决于激活的FGFR信号传导,同时抑制FGF受体底物2α(FRS2α)磷酸化。在同系小鼠肿瘤模型中，与任何一种单独治疗相比，仑伐替尼(Lenvatinib)和抗PD-1单克隆抗体联用减少了与肿瘤相关的巨噬细胞，增加激活的细胞毒性T细胞，并表现出更强的抗肿瘤活性。仑伐替尼(Lenvatinib)与依维莫司(Everolimus)联合用药体外可抑制人内皮细胞增殖、血管形成、
Lestaurtinib 来他替尼 Lestaurtinib inhibits autophosphorylation of FMS-like tyrosine kinase 3 (FLT3), resulting in inhibition of FLT3 activity and induction of apoptosis in tumor cells that overexpress FLT3. Lestaurtinib抑制FMS样酪氨酸激酶3（FLT3）的自磷酸化，从而抑制FLT3活性并诱导过表达FLT3的肿瘤细胞凋亡。 2021/11/26 D0078
Lorlatinib 洛拉替尼 Lorbrena 博瑞纳 辉瑞 2018/11/2 FDA/NMPA LORBRENA is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. LORBRENA是一种激酶抑制剂，适用于间变性淋巴瘤激酶(ALK)阳性的转移性非小细胞肺癌(NSCLC)成人患者。2022年NMPA批准洛拉替尼适用于间变性淋巴瘤激酶(ALK)阳性的局部晚期或转移性非小细胞肺癌(NSCLC)患者的治疗。 非小细胞肺癌 Non-small cell lung cancer (NSCLC) accounts for up to 85% of lung cancer cases worldwide and remains a particularly difficult to treat condition. The gene rearrangement of anaplastic lymphoma kinase (ALK) is a genetic alteration that drives the development of NSCLC in a number of patients(PubMed:18097461,PubMed:25914136). Ordinarily, ALK is a natural endogenous tyrosine kinase receptor that plays an important role in the development of the brain and elicits activity on various specific neurons in the nervous system(PubMed:29101158,PubMed:29067878,PubMed:18097461).Subsequnetly, lorlatinib is a kinase inhibitor with in vitro activity against ALK and number of other tyrosine kinase receptor related targets including ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. Moreover, lorlatinib possesses the capability to cross the blood-brain barrier, allowing it to reach and treat progressive or worsening brain metastases as well(PubMed:29067878). The overall antitumor activity of lorlatinib in in-vivo models appears to be dose-dependent and correlated with the inhibition of ALK phosphorylation.Although many ALK-positive metastatic NSCLC patients respond to initial tyrosine kinase therapies, such patients also often experience tumor progression(PubMed:28122866). Various clinical trials performed with lorlatinib, however, have demonstrated its utility to effect tumor regression in ALK-positive metastatic NSCLC patients who experience tumor progression despite current use or having already used various first and second-generation tyrosine kinase inhibitors like crizotinib, alectinib, or ceritinib(PubMed:30413381). 非小细胞肺癌（NSCLC）占全球肺癌患者的85%，并且仍然是特别难以治疗的疾病。间变性淋巴瘤激酶（ALK）基因重排的遗传变异可驱动许多患者的NSCLC发展（PubMed: 18097461, PubMed: 25914136）。通常情况下，ALK是一种天然的内源性酪氨酸激酶受体，在大脑发育中起着重要作用，并在神经系统的各种特异神经元上发挥活性（PubMed: 29101158, PubMed: 29067878, PubMed: 18097461）。相应地，劳拉替尼（Lorlatinib）是一种激酶抑制剂，对ALK具有体外活性，并可靶向多种其他酪氨酸激酶受体，包括ROS1、TYK1、FER、FPS、TRKA、TRKB、TRKC、FAK、FAK2和ACK。劳拉替尼（Lorlatinib）对多种ALK突变酶表现出体外活性，包括在克唑替尼（Crizotinib）和其他ALK抑制剂治疗下疾病进展的肿瘤中检测到的突变。此外，劳拉替尼（Lorlatinib）血脑屏障通透性高，能够治疗进行性或恶化性脑转移非小细胞肺癌（PubMed: 29067878）。劳拉替尼（Lorlatinib）在体内模型的整体抗肿瘤活性呈剂量依赖性，并与抑制ALK磷酸化有关。尽管多数ALK阳性转移性NSCLC患者对最初的酪氨酸激酶疗法产生响应，但是后期这些患者的病情通常会发现再度恶化（PubMed: 28122866）。然而，多项劳拉替尼（Lorlatinib）的临床试验表明，对于正在或已使用各种第一、二代酪氨酸激酶抑制剂（如克唑替尼[Crizotinib]、阿来替尼[Alectinib]或色瑞替尼[Ceritinib]）后肿瘤进展的ALK阳性转移性NSCLC患者，其可有效促进患者的肿瘤消退（PubMed: 30413381）。 FDA-appr
M2698 M2698 can cross the blood-brain barrier and has anti-cancer activity. M2698 is an orally active, ATP competitive, selective p70S6K and Akt dual-inhibitor with IC50s of 1 nM for p70S6K, Akt1 and Akt3.The mean total concentration of M2698 after 16-hour infusion in rats is 1750 ng/g and 175 ng/mL in brain and plasma, respectively. M2698 (po; 1, 5, 10, or 20 mg/kg/day; for 7 days) inhibits the phosphorylation of S6 in a dose-proportional manner over time after a single administration or daily treatments over 7 days. M2698 (10-30 mg/kg/day; PO; 28 days) results in dose-dependent inhibition of tumor growth and results in tumor regression with the highest dose of 30 mg/kg. M2698 (20 mg/kg/day; PO; 4 days) has a tumor:plasma exposure ratio of 12:1 over 24 hours and leads to increased levels of pAkt in tumor tissue.M2698 (0.3, 1 μM; 24 hours) inhibits p70S6K activity and induces feedback loop phosphorylation on Akt and suppresses Akt activity in breast cancer cell lines. M2698 inhibits indirectly pGSK3β (IC50=17 nM) and pS6 (IC50=15 nM). M2698 (0.3 nM to 50 M; 72 hours) inhibits proliferation in a dose-dependent manner in breast tumors cell lines with IC50s of 0.02-8.5 μM. M2698可穿越血脑屏障并具有抗癌活性。M2698是一种具有口服活性，ATP竞争性的选择性p70S6K和Akt双重抑制剂，对p70S6K、Akt1和Akt3的IC50值为1 nM。注入大鼠16小时后，M2698的脑部和血浆药物平均总浓度分别为1750 ng/g和175 ng/mL。M2698（口服；1、5、10或20 mg/kg/天；持续7天）在单次给药或持续7天以上的日常治疗后，会随时间成剂量比例地抑制S6的磷酸化。M2698（10-30 mg/kg/天；口服；28天）剂量依赖性地抑制肿瘤生长，并在最高剂量30 mg/kg下导致肿瘤消退。M2698（20 mg/kg/天；口服；4天）在24小时后的肿瘤/血浆暴露比为12：1，并导致肿瘤组织中pAkt的水平升高。M2698（0.3，1 μM；24小时）抑制p70S6K活性并诱导Akt的反馈性磷酸化，并抑制乳腺癌细胞系中Akt的活性。M2698可以间接抑制pGSK3β（IC50 = 17 nM）和pS6（IC50 = 15 nM）。M2698（0.3 nM至50 M；72小时）可剂量依赖性地抑制乳腺肿瘤细胞系中的增殖，IC50值为0.02-8.5 μM。 2021/11/26 D0081
Midostaurin 米哚妥林 Rydapt 诺华制药 2017/4/28 FDA RYDAPT is a kinase inhibitor indicated for the treatment of adult patients with:1. Newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation positive as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation. 2.Aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL). RYDAPT是一种激酶抑制剂，其适应症为：1.与标准的阿糖胞苷和柔红霉素诱导及阿糖胞苷巩固相结合，治疗新诊FLT3突变阳性急性髓系白血病(AML)成人患者；2.侵袭性系统性肥大细胞增多症(ASM)、伴有相关血液肿瘤的系统性肥大细胞增多症(SM-AHN)或肥大细胞白血病(MCL)成人患者。 急性髓系白血病、肥大细胞增多症 It potently inhibits multiple receptor tyrosine kinases. Midostaurin and its major active metabolites CGP62221 and CGP52421 inhibit the activity of protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and WT and/or mutant FLT3 tyrosine kinases. Inhibition of FLT3 receptor signalling cascades induces apoptosis of target leukemia cells expressing target receptors and mast cells, in addition to its antiproliferative activity toward multiple cancer cell lines(PubMed:27186148).Midostaurin also interacts with organic anion transporter (OATP) 1A1 and multidrug resistance protein (MRP)-2 according to preliminary in vitro studies. 该药物有效抑制多种受体酪氨酸激酶。 Midostaurin及其主要活性代谢物CGP62221和CGP52421可以抑制蛋白激酶Cα（PKCalpha）、VEGFR2、KIT、PDGFR以及野生型和/或突变型FLT3酪氨酸激酶的活性。抑制FLT3受体信号级联反应不仅可诱导表达靶受体的白血病细胞和肥大细胞细胞凋亡，而且还具有抗多种癌细胞增殖作用（PubMed: 27186148）。根据初步的体外研究，Midostaurin还可以与有机阴离子转运蛋白（OATP）1A1和多药耐药相关蛋白（MRP）-2相互作用。 04/2021 2021/11/26 D0082
Milademetan Milademetan is under investigation in clinical trial NCT02319369 (Safety, Tolerability and Pharmacokinetics of Milademetan Alone and With 5-Azacitidine (AZA) in Acute Myelogenous Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)). Milademetan（DS-3032/RAIN-32）是一种MDM2-p53相互作用的选择性小分子抑制剂，在体外能以纳摩尔级别的浓度激活p53功能。在临床前研究中，milademetan可诱导人类癌细胞系的p53依赖性凋亡，并在具有功能性野生型p53的肿瘤异种移植模型中显示出抗肿瘤活性。 Milademetan正在进行临床试验NCT02319369（Milademetan单药以及联用阿扎胞苷[5-Azacitidine，AZA]在急性髓性白血病（AML）或高危骨髓增生异常综合征（MDS）中的安全性、耐受性和药代动力学研究）。 230919 pj D0083 新增作用机制内容 LXL
Neratinib 奈拉替尼 Nerlynx 贺俪安 Puma Biotechnology, Inc 2017-07-17 00:00:00 FDA/NMPA NERLYNX is a kinase inhibitor indicated: 1.As a single agent, for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy. 2. In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting. NERLYNX是一种激酶抑制剂，其适应症为：1.单药用于经以曲妥珠单抗为基础辅助治疗的早期HER2阳性乳腺癌成人患者的延长辅助治疗。2.联合卡培他滨用于治疗既往接受过两种或两种以上的基于抗HER2治疗方案的转移性晚期或转移性HER2阳性乳腺癌患者。2020年4月NMPA批准贺俪安（马来酸奈拉替尼片）用于人类表皮生长因子受体 2（HER2）阳性的早期乳腺癌成年患者，在接受含曲妥珠单抗辅助治疗之后的强化辅助治疗。 乳腺癌 Neratinib is an intracellular kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), HER2, and HER4. In vitro, neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Neratinib human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2, and HER4 in vitro. In vivo, oral administration of neratinib inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR. 奈拉替尼（Neratinib）是一种胞内蛋白激酶抑制剂，可以不可逆地与表皮生长因子受体（EGFR）、HER2和HER4结合。在体外试验中，奈拉替尼（Neratinib）降低了EGFR和HER2的自磷酸化以及下游MAPK和AKT信号传导，并在表达EGFR和/或HER2癌细胞系中显示抗肿瘤活性。奈拉替尼（Neratinib）的人体代谢产物M3、M6、M7和M11在体外也可以抑制EGFR、HER2和HER4的活性。在表达HER2和EGFR肿瘤细胞系的小鼠异种移植模型中，口服奈拉替尼（Neratinib）可以抑制肿瘤生长。 06/2021 230814 pj D0085 机制描述中药物中文名称订正 LXL
Nilotinib 尼洛替尼 Tasigna 达希纳 诺华制药 2007/11/2 FDA/NMPA Tasigna is a kinase inhibitor indicated for the treatment of: 1.Adult and pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. 2.Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+ CML resistant to or intolerant to prior therapy that included imatinib. 3.Pediatric patients greater than or equal to 1 year of age with Ph+ CML-CP and CML-AP resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy. Tasigna是一种激酶抑制剂，其适应症包括：1.初诊为费城染色体阳性慢性髓系白血病(Ph+ CML)慢性期的成人和儿童(≥1岁)患者。2.包括伊马替尼在内的既往治疗耐药或不耐受的慢性期(CP)和加速期(AP) Ph+ CML成人患者。3.对酪氨酸激酶抑制剂(TKI)既往治疗耐药或不耐受的Ph+ CML-CP和CML-AP儿童(≥1岁)患者。 慢性髓系白血病 Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein. In vitro, nilotinib inhibited BCR-ABL mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Ph+ CML. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 out of 33 mutations tested. Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: BCR-ABL (20 to 60 nM), PDGFR (69 nM), c-KIT (210 nM), CSF-1R (125 to 250 nM), and DDR1(3.7 nM). 尼洛替尼（Nilotinib）是一种BCR-ABL激酶抑制剂。尼洛替尼（Nilotinib）可结合并稳定ABL蛋白激酶位点的非活性构象。在体外，尼洛替尼（Nilotinib）抑制BCR-ABL激酶介导的鼠白血病细胞系和Ph+CML患者细胞系的增殖。在33个检测的突变中，尼洛替尼（Nilotinib）能克服32个BCR-ABL激酶突变造成的伊马替尼（Imatinib）耐药。尼洛替尼（Nilotinib）能够抑制以下这些激酶的自磷酸化（另附IC50值）：BCR-ABL（20-60 nM）、PDGFR（69 nM）、c-Kit（210 nM）、CSF-1R（125-250 nM）以及DDR1（3.7 nM）。 09/2021 2021/11/26 D0086
Niraparib 尼拉帕利 Zejula 则乐 葛兰素史克 2017/3/27 FDA/NMPA ZEJULA is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated:1.for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy. 2.for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. ZEJULA是一种聚(ADP-核糖)聚合酶(PARP)抑制剂，其适应症包括：1.对一线铂类化疗完全或部分反应的晚期卵巢上皮癌、输卵管癌或原发性腹膜癌成人患者的维持治疗。2.对铂类化疗完全或部分反应的携带有害或疑似有害BRCA胚系突变的复发性卵巢上皮癌，输卵管癌或原发性腹膜癌成人患者的维持治疗。2019年NMPA批准本品适用于铂敏感的复发性上皮性卵巢癌、输卵管癌或原发性腹膜癌成人患者在含铂化疗达到完全缓解或部分缓解后的维持治疗。2020年NMPA批准本品适用于晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌成人患者对一线含铂化疗达到完全缓解或部分缓解后的维持治疗。 卵巢癌、输卵管癌、原发性腹膜癌 Niraparib is an inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2, which play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis and cell death. Increased niraparib-induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient-derived xenograft tumor models with homologous recombination deficiency that had either mutated or wild type BRCA1/2. 尼拉帕利（Niraparib）是聚（ADP-核糖）聚合酶（PARP）PARP-1和PARP-2抑制剂，它们在DNA修复中起作用。体外研究表明，尼拉帕利（Niraparib）诱导的细胞毒性可能涉及PARP酶活性抑制和PARP-DNA复合物形成增加，从而导致DNA损伤、凋亡和细胞死亡。在BRCA1/2有或无缺陷的肿瘤细胞系中可观察到尼拉帕利（Niraparib）诱导的细胞毒性增强。在BRCA1/2缺陷型人源肿瘤细胞系的小鼠异种移植模型，以及在带有突变或野生型BRCA1/2的同源重组缺陷的患者源性异种移植肿瘤模型中，尼拉帕利（Niraparib）可降低肿瘤的生长。 FDA-approval:12/202203/2021;NMPA-approval:2020 2023/6/20 sxz D0087
Nivolumab 纳武利尤单抗 Opdivo 欧狄沃 百时美施贵宝 2014/12/22 FDA/NMPA OPDIVO is a programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of: 1.Melanoma :(1)patients with unresectable or metastatic melanoma, as a single agent or in combination with ipilimumab.(2)patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting.2.Non-Small Cell Lung Cancer (NSCLC):(1).adult patients with metastatic non-small cell lung cancer expressing PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with ipilimumab. (2).adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations as first-line treatment, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy. (3).patients with metastatic non-small cell lung cancer and progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO. 3.Malignant Pleural Mesothelioma:adult patients with unresectable malignant pleural mesothelioma, as first-line treatment in combination with ipilimumab. 4.Renal Cell Carcinoma (RCC):(1).patients with intermediate or poor risk advanced renal cell carcinoma, as a first-line treatment in combination with ipilimumab. (2）.patients with advanced renal cell carcinoma, as a first-line treatment in combination with cabozantinib. (3).patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy. 5.Classical Hodgkin Lymphoma (cHL).(1).adult patients with classical Hodgkin lymphoma that has relapsed or progressed aftera: autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or 3 or more lines of systemic therapy that includes autologous HSCT. 6.Squamous Cell Carcinoma of the Head and Neck (SCCHN).(1).patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy.7.Urothelial Carcinoma:(1).adjuvant treatment of patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC. (2).patients with locally advanced or metastatic urothelial carcinoma who: have disease progression during or following platinum-containing chemotherapy orchave disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. 8.Colorectal Cancer.(1).adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, as a single agent or in combination with ipilimumab. 9.Hepatocellular Carcinoma (HCC):patients with hepatocellular carcinoma who have been previously treated with sorafenib in combination with ipilimumab. 10.Esophageal Cancer:(1). patients with completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease, who have received neoadjuvant chemoradiotherapy (CRT). (2).patients with unresectable advanced or metastatic esophageal squamous cell carcinoma as first-line treatment in combination with fluoropyrimidine- and platinum-containing chemotherapy.（3）.patients with unresectable advanced or metastatic esophageal squamous cell carcinoma as first-line treatment in combination with ipilimumab.(4)patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. OPDIVO是一种程序性死亡受体1(PD-1)阻断抗体，其适应症包括：1.黑色素瘤：(1)单药或联合伊匹单抗用于治疗不可切除性或转移性黑色素瘤。(2)既往辅助治疗时接受完全切除后伴有淋巴结受累或转移性疾病
Olaparib 奥拉帕利 Lynparza 利普卓 阿斯利康 2014/12/19 FDA/NMPA Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated: Ovarian cancer for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. in combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either: a deleterious or suspected deleterious BRCA mutation, and/or genomic instability.Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Breast cancer for the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. for the treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. Pancreatic cancer for the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. Prostate cancer. for the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. Lynparza是一种聚(ADP-核糖)聚合酶(PARP)抑制剂，其适应症包括：1.卵巢癌。(1)用于携带有害或疑似有害的胚系或体细胞BRCA突变的晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌成人患者在一线含铂化疗达到完全或部分缓解(CR/PR)后的维持治疗。(2)联合贝伐单抗用于晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌成人患者在一线含铂化疗达到完全或部分缓解(CR/PR)后的维持治疗，这些患者与携带有害或疑似有害BRCA突变和/或基因组不稳定导致的同源重组缺陷(HRD)阳性状态相关。(3)用于复发性上皮性卵巢癌、输卵管癌或原发性腹膜癌成人患者在一线含铂化疗达到完全或部分缓解(CR/PR)后的维持治疗。2.乳腺癌：（1）用于携带有害或疑似有害胚系BRCA突变（gBRCAm）、HER2阴性的高危早期乳腺癌成人患者的辅助治疗，这些患者已接受过新辅助或辅助<E8BE85><E58AA9>
Osimertinib 奥希替尼 Tagrisso 泰瑞沙 阿斯利康 2015/11/13 FDA/NMPA TAGRISSO is a kinase inhibitor indicated for:1.as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test。 2.he first-line treatment of adult patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. 3.the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR TKI therapy. TAGRISSO是一种激酶抑制剂，其适应症为：1 .用于表皮生长因子受体(EGFR)19号外显子缺失或21号外显子L858R突变的非小细胞肺癌(NSCLC)成人患者肿瘤切除术后的辅助治疗。2.表皮生长因子受体(EGFR)19号外显子缺失或21号外显子L858R突变的转移性NSCLC的一线治疗。3.EGFR T790M突变阳性、EGFR TKI治疗期间或之后疾病进展的转移性NSCLC成人患者。2017年奥希替尼首次获得NMPA批准，至2022年为止NMPA批准其适用于非小细胞肺癌患者的治疗。 非小细胞肺癌 Osimertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) at approximately 9- fold lower concentrations than wild-type. Two pharmacologically-active metabolites (AZ7550 and AZ5104 circulating at approximately 10% of the parent) with similar inhibitory profiles to osimertinib have been identified in the plasma after oral administration of osimertinib. AZ7550 showed a similar potency to osimertinib, while AZ5104 showed greater potency against exon 19 deletion and T790M mutants (approximately 8-fold) and wild-type (approximately 15-fold) EGFR. In vitro, osimertinib also inhibited the activity of HER2, HER3, HER4, ACK1, and BLK at clinically relevant concentrations.In cultured cells and animal tumor implantation models, osimertinib exhibited anti-tumor activity against NSCLC lines harboring EGFR-mutations (T790M/L858R, L858R, T790M/exon 19 deletion, and exon 19 deletion) and, to a lesser extent, wild-type EGFR amplifications. Osimertinib distributed to the brain in multiple animal species (monkey, rat, and mouse) with brain to plasma AUC ratios of approximately 2 following oral dosing. These data are consistent with observations of tumor regression and increased survival in osimertinib- versus control-treated animals in a pre-clinical mutant-EGFR intracranial mouse metastasis xenograft model (PC9; exon 19 deletion). 奥西替尼（Osimertinib）是一种表皮生长因子受体（EGFR）激酶抑制剂，能以比野生型低约9倍的浓度与某些EGFR突变（T790M，L858R和外显子19缺失）不可逆地结合。口服奥西替尼（Osimertinib）后在血浆中发现两种具有药理活性的代谢物（AZ7550和AZ5104，约占前体药物的10%），其抑制作用与奥西替尼相似。AZ7550与奥西替尼（Osimertinib）的效力相似，而AZ5104对EGFR 19号外显子缺失、T790M突变（约8倍）以及野生型EGFR（约15倍）的活性较强。体外试验显示，奥西替尼（Osimertinib）在临床浓度下也能抑制HER2、HER3、HER4、ACK1和BLK的活性。在细胞培养和动物肿瘤移植瘤模型中，奥希替尼（Osimertinib）对携带EGFR突变（T790M/L858R、L858R、T790M/19号外显子缺失、19号外显子缺失）的非小细胞肺癌（NSCLC）细胞系具有抗肿瘤活性，对野生型EGFR基因扩增的抗肿瘤活性较弱。奥西替尼（Osimertinib）口服给药后高分布于多种动物（猴子，大鼠和小鼠）的脑部，其脑-血AUC比约为2：1。这些数据与一项临床前研究结果一致：在EGFR突变小鼠异种颅内移植模型（PC9；19号外显子缺失）中，与对照组相比，可观察到奥西替尼（Osimertinib）组的肿瘤消退以及存活率提高<E68F90><E9AB98>
Birabresib Birabresib is under investigation in clinical trial NCT02698176 (A Dose Exploration Study With MK-8628 in Participants With Selected Advanced Solid Tumors (MK-8628-006)). Birabresib (OTX-015) 是一种有效的 BRD2/3/4 抑制剂，IC50 值为 92-112 nM。 Birabresib正处于临床试验NCT02698176（MK-8628在某些晚期实体瘤受试者中的剂量探索研究（MK-8628-006））。 231008 pj D0091 新增作用机制内容 LXL
Palbociclib 哌柏西利 Ibrance 爱博新 PfizerEuropeMAEEIG 2015/11/13 FDA/NMPA IBRANCE is a kinase inhibitor indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with: 1.an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or in men. 2.fulvestrant in patients with disease progression following endocrine therapy. BRANCE是一种激酶抑制剂，适用于激素受体( hormone receptor，HR )阳性、人表皮生长因子受体2 ( human epidermal growth factor receptor 2，HER2 )阴性的晚期或转移性乳腺癌成年患者：IBRANCE是一种激酶抑制剂，其适应症为：1.联合芳香化酶抑制剂用于初始内分泌治疗。2.与氟维司群联用用于治疗内分泌治疗后疾病进展的患者。2018年NMPA批准哌柏西利适用于乳腺癌患者的治疗。 乳腺癌 Palbociclib is an inhibitor of cyclin-dependent kinases (CDK)4 and 6. Cyclin D1 and CDK4/6 are downstream of signaling pathways which lead to cellular proliferation. In vitro, palbociclib reduced cellular proliferation of estrogen receptor(ER)-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle. Treatment of breast cancer cell lines with the combination of palbociclib and antiestrogens leads to decreased retinoblastoma(Rb) protein phosphorylation resulting in reduced E2F expression and signaling, and increased growth arrest compared to treatment with each drug alone. In vitro treatment of ER-positive breast cancer cell lines with the combination of palbociclib and antiestrogens led to increased cell senescence compared to each drug alone, which was sustained for up to 6 days following palbociclib removal and was greater if antiestrogen treatment was continued. In vivo studies using a patient-derived ER-positive breast cancer xenograft model demonstrated that the combination of palbociclib and letrozole increased the inhibition of Rb phosphorylation, downstream signaling, and tumor growth compared to each drug alone.Human bone marrow mononuclear cells treated with palbociclib in the presence or absence of an anti-estrogen in vitro did not become senescent and resumed proliferation following palbociclib withdrawal. 哌柏西利（Palbociclib）是周期蛋白依赖性激酶（CDK）4和6的抑制剂。细胞周期蛋白D1和CDK4/6是细胞增殖相关信号通路的下游效应蛋白。体外试验表明，哌柏西利（Palbociclib）通过阻断细胞从细胞周期G1进入S期，来减少雌激素受体（ER）阳性乳腺癌细胞系的增殖。与单独各个药物相比，哌柏西利（Palbociclib）和抗雌激素联用可降低乳腺癌细胞系中视网膜母细胞瘤蛋白（Rb）磷酸化，从而减少E2F表达和信号传导，促进生长停滞。体外试验表明，哌柏西利（Palbociclib）和抗雌激素联合相比各单药，可以加速ER阳性乳癌细胞系衰老，哌柏西利（Palbociclib）停药后6天仍有效果，若继续使用抗雌激素治疗则效果更好。一项患者源性ER阳性乳腺癌异种移植模型的体内研究表明，与单独各种药物相比，哌柏西利（Palbociclib）和来曲唑（Letrozole）联合可加强抑制Rb磷酸化、下游信号传导以及肿瘤生长。无论是否联合抗雌激素，哌柏西利（Palbociclib）体外处理的人骨髓单核细胞在停药后不会衰老和恢复增殖。 FDA-approval:12/2022 2023/6/20 sxz D0092 修改适应证 pj
Panitumumab 帕尼单抗 Vectibix 安进 2006/9/27 FDA Vectibix is an epidermal growth factor receptor (EGFR) antagonist indicated for the treatment of wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC):1.In combination with FOLFOX for first-line treatment.2.As monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy. Vectibix是一种表皮生长因子受体(EGFR)拮抗剂，其适应症为：1.联合FOLFOX用于RAS野生型(KRAS和NRAS均为野生型)转移性结直肠癌(mCRC)的一线治疗。2.单药用于治疗既往接受含氟嘧啶类、奥沙利铂和伊立替康化疗后疾病进展的RAS野生型mCRC。 结直肠癌 The EGFR is a transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine kinases, including EGFR, HER2, HER3, and HER4. EGFR is constitutively expressed in normal epithelial tissues, including the skin and hair follicle. EGFR is overexpressed in certain human cancers, including colon and rectum cancers. Interaction of EGFR with its normal ligands (e.g., EGF, transforming growth factor-alpha) leads to phosphorylation and activation of a series of intracellular proteins, which in turn regulate transcription of genes involved with cellular growth and survival, motility, and proliferation. KRAS (Kirsten rat sarcoma 2 viral oncogene homologue) and NRAS (Neuroblastoma RAS viral oncogene homologue) are highly related members of the RAS oncogene family. Signal transduction through the EGFR can result in activation of the wild-type KRAS and NRAS proteins; however, in cells with activating RAS somatic mutations, the RAS-mutant proteins are continuously active and appear independent of EGFR regulation.Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased proinflammatory cytokine and vascular growth factor production, and internalization of the EGFR. In vitro assays and in vivo animal studies demonstrate that panitumumab inhibits the growth and survival of selected human tumor cell lines expressing EGFR. 跨膜糖蛋白EGFR是I型受体酪氨酸激酶（包括EGFR，HER2，HER3和HER4）亚家族的成员。EGFR在包括皮肤和毛囊在内的正常上皮组织中组成性表达。某些人类癌症（包括结肠癌和直肠癌）中EGFR过表达。EGFR与其正常配体（例如EGF、转化生长因子-α）的相互作用导致一系列胞内蛋白的磷酸化和激活，继而调节与细胞生长、存活、运动性以及增殖相关基因的转录。KRAS（Kirsten大鼠肉瘤病毒癌基因同源物）和NRAS（神经母细胞瘤RAS病毒癌基因同源物）是RAS癌基因家族中高度相关的成员。通过EGFR的信号转导可导致野生型KRAS和NRAS蛋白激活。然而，在具有RAS体细胞激活突变的细胞中，RAS突变蛋白处于持续激活状态，不依赖EGFR的调控。帕尼单抗（Panitumumab）可以与正常细胞和肿瘤细胞上的EGFR特异性结合，并竞争性抑制EGFR配体的结合。非临床研究表明，帕尼单抗（Panitumumab）与EGFR结合可阻止配体诱导的受体自磷酸化和受体相关激酶的激活，从而抑制细胞生长、诱导细胞凋亡、减少促炎细胞因子和血管生长因子的产生以及EGFR的内在化。体外试验和体内动物研究表明，帕尼单抗（Panitumumab）可以抑制某些表达EGFR人类肿瘤细胞系的生长和存活。 08/2021 2021/11/26 D0094
Pazopanib 培唑帕尼 Votrient 维全特 葛兰素史克 2009/10/19 FDA/NMPA VOTRIENT is a kinase inhibitor indicated for the treatment of adults with:1.advanced renal cell carcinoma (RCC). 2.advanced soft tissue sarcoma (STS) who have received prior chemotherapy. VOTRIENT是一种激酶抑制剂，适用于晚期肾细胞癌(RCC)和既往接受过化疗的晚期软组织肉瘤(STS)成人患者。 肾细胞癌、软组织肉瘤 Pazopanib is a multi-tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, fibroblast growth factor receptor (FGFR)-1 and -3, cytokine receptor (Kit), interleukin-2 receptor-inducible T-cell kinase (Itk), lymphocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c- Fms). In vitro, pazopanib inhibited ligand-induced autophosphorylation of VEGFR-2, Kit, and PDGFR- receptors. In vivo, pazopanib inhibited VEGF-induced VEGFR-2 phosphorylation in mouse lungs, angiogenesis in a mouse model, and the growth of some human tumor xenografts in mice. 培唑帕尼（Pazopanib）是血管内皮生长因子受体（VEGFR）-1/2/3，血小板衍生生长因子受体（PDGFR）-α/β，成纤维细胞生长因子受体（FGFR）-1/3，细胞因子受体（Kit），白介素2受体诱导的T细胞激酶（Itk），淋巴细胞特异性蛋白酪氨酸激酶（Lck）和跨膜糖蛋白受体酪氨酸激酶（c-Fms）的多靶点酪氨酸激酶抑制剂。 在体外，培唑帕尼（Pazopanib）抑制配体诱导的VEGFR-2、Kit和PDGFR-β受体自身磷酸化。 在体内，培唑帕尼（Pazopanib）抑制小鼠肺中VEGF诱导的VEGFR-2磷酸化、小鼠模型的血管生成以及小鼠中某些人源肿瘤异种移植物的生长。 09/2021 2021/11/26 D0095
Pemigatinib 佩米替尼 Pemazyre 达伯坦 Incyte Biosciences Distribution B.V. 2020/4/17 0:00 FDA/NMPA PEMAZYRE is a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement.For the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. 佩米替尼是一种激酶抑制剂，适用于1.既往接受过治疗、伴有成纤维细胞生长因子受体2(FGFR2)融合或其他重排的不可切除性局部晚期或转移性胆管癌。2.伴有FGFR1重排的复发或难治性髓系/淋巴样肿瘤(MLNs)的成人患者。2022年NMPA批准佩米替尼用于既往至少接受过一种系统性治疗，且经检测确认存在有 FGFR2 融合或重排的晚期、转移性或不可手术切除的胆管癌成人患者的治疗。 胆管癌 Pemigatinib is a small molecule kinase inhibitor that targets FGFR1, 2 and 3 with IC50 values of less than 2 nM. Pemigatinib also inhibited FGFR4 in vitro at a concentration approximately 100 times higher than those that inhibit FGFR1, 2, and 3. Pemigatinib inhibited FGFR1-3 phosphorylation and signaling and decreased cell viability in cancer cell lines with activating FGFR amplifications and fusions that resulted in constitutive activation of FGFR signaling. Constitutive FGFR signaling can support the proliferation and survival of malignant cells.Pemigatinib exhibited anti-tumor activity in mouse xenograft models of human tumors with FGFR1, FGFR2, or FGFR3 alterations resulting in constitutive FGFR activation including a patient-derived xenograft model of cholangiocarcinoma that expressed an oncogenic FGFR2- Transformer-2 beta homolog (TRA2b) fusion protein. Pemigatinib是一种靶向FGFR1、2和3的小分子激酶抑制剂，IC50值小于2 nM。培米替尼（Pemigatinib）还能在体外抑制FGFR4，浓度比抑制FGFR1、2和3的浓度高约100倍。在FGFR扩增和融合导致FGFR信号组成性激活的肿瘤细胞系中，培米替尼（Pemigatinib）可以抑制FGFR1-3磷酸化和信号传导并降低细胞活力。组成性激活的FGFR信号可以促进恶性细胞的增殖和存活。培米替尼（Pemigatinib）在FGFR1、FGFR2或FGFR3基因改变导致FGFR组成性激活的人源肿瘤小鼠异种移植模型（包括一种表达FGFR2-转化因子2β同源物（TRA2b）融合蛋白的患者源性胆管癌异种移植模型）中表现出抗肿瘤活性。 FDA-approval: 08/2022；NMPA-approval: 03/2022 231107 pj D0097 商品名修改 SXZ
Pertuzumab 帕妥珠单抗 Perjeta 帕捷特 罗氏制药 2012/6/8 FDA/NMPA PERJETA是一种HER2/neu受体拮抗剂，其适应症为：1.联合曲妥珠单抗和多西紫杉醇用于治疗既往未接受过抗HER2治疗或转移性疾病化疗的HER2阳性转移性乳腺癌(MBC)。2.联合曲妥珠单抗和化疗用于：(1)HER2阳性的局部晚期、炎性或早期乳腺癌(直径大于2cm或淋巴结阳性)的新辅助治疗，作为早期乳腺癌整体治疗方案的一部分。(2)具有复发高风险的HER2阳性早期乳腺癌的辅助治疗。2018年NMPA批准帕妥珠单抗和化疗联合作为具有高复发风险 HER2 阳性早期乳腺癌患者的辅助治疗。2019年NMPA批准帕妥珠单抗与曲妥珠单抗和多西他赛联合，适用于HER2 阳性、转移性或不可切除的局部复发性乳腺癌患者。 乳腺癌 Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3, and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein (MAP) kinase, and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity (ADCC).While pertuzumab alone inhibited the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab augmented anti-tumor activity in HER2-overexpressing xenograft models. 帕妥珠单抗（Pertuzumab）靶向细胞外人表皮生长因子受体2蛋白（HER2）的二聚化结构域（子结构域Ⅱ），从而阻断HER2与其它HER家族成员（包括EGFR、HER3和HER4）的配体依赖性异源二聚化作用。结果，帕妥珠单抗（Pertuzumab）通过两条主要信号途径（有丝分裂原激活蛋白[MAP]激酶和磷酸肌醇3激酶[PI3K]）抑制配体启动的细胞内信号传导。这些信号通路的抑制分别导致细胞生长停滞和凋亡。此外，帕妥珠单抗（Pertuzumab）介导抗体依赖性细胞介导的细胞毒性作用（ADCC）。尽管单独使用帕妥珠单抗（Pertuzumab）能抑制人肿瘤细胞的增殖，但在过表达HER2的异种移植模型中，帕妥珠单抗（Pertuzumab）和曲妥珠单抗（Trastuzumab）联合可以增强抗肿瘤活性。 FDA-approval:01/2020；NMPA-approval:2018；NMPA-approval:2019 2023/6/20 sxz D0098
Pexidartinib Turalio 第一三共株式会社 2019/8/2 FDA TURALIO is a kinase inhibitor indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. URALIO是一种激酶抑制剂，用于治疗患有症状性腱鞘巨细胞瘤(TGCT)的成人患者，这些患者症状发生率高或造成严重功能性限制，且无法通过手术改善。 腱鞘巨细胞瘤 Tenosynovial giant cell tumor is a rare, non-malignant neoplasm that causes abnormal growth and damage to the synovium, bursae, or tendon sheaths.Recruitment of immune cells, specifically macrophages, is closely associated with the tumor mass formation in tenosynovial giant cell tumors(PubMed:30002809).Macrophages drive tumor-promoting inflammation(PubMed:28117416).and play a central role in every stage of tumor progression(PubMed:28210073).As the most abundant immune cells in the tumor microenvironment of solid tumors, macrophages promote processes that enhance tumor survival, such as angiogenesis, tumor cell invasion, and intravasation at the primary site(PubMed:28210073).They also modulate the immune response to tumors to inhibit tumor clearance and directly engage with tumor cells to activate pro-survival signaling pathways(PubMed:17527089).The recruitment, proliferation, and irreversible differentiation of macrophages are regulated by colony-stimulating factor-1 (CSF-1)(PubMed:28716061,PubMed:22186992).which is a cytokine that is often translocated and highly expressed in tenosynovial giant cell tumors(PubMed:17527089).Elevated expression of CSF-1 and CSF-1 receptor (CSF1R) has also been implicated in various models of malignant cancers and tumors(PubMed:19443701).Pexidartinib targets the CSF1/CSF1R pathway as a selective CSF1R inhibitor. It stimulates the autoinhibited state of the CSF1R by interacting with the juxtamembrane region of CSF1R, which is responsible for folding and inactivation of the kinase domain, and preventing the binding of CSF1 and ATP to the region(PubMed:30002809).Without the binding of CSF1 to the receptor, CSF1R cannot undergo ligand-induced autophosphorylation.By inhibiting the CSF1R signaling pathway, pexidartinib works to inhibit tumor cell proliferation and downmodulate cells involved in the disease, such as macrophages. It was also shown to inhibit the CD117 or proto-oncogene receptor tyrosine kinase (cKIT), mutant fms-like tyrosine kinase 3 (FLT3), and platelet-derived growth factor receptor (PDGFR)-β, which are all receptor tyrosine kinases that regulate critical cellular processes such as cell proliferation and survival(PubMed:28716061). 腱鞘巨细胞瘤是一种罕见的良性软组织肿瘤，会导致滑膜、法氏囊或腱鞘的异常生长并受损。免疫细胞特别是巨噬细胞的募集与腱鞘巨细胞瘤肿块的形成密切相关(PubMed:30002809)。巨噬细胞可驱动促进肿瘤的炎症(PubMed:28117416)。并在肿瘤进展的每个阶段中起着核心作用(PubMed:28210073)。作为实体瘤的肿瘤微环境中最丰富的免疫细胞，巨噬细胞可促进增强肿瘤存活的进程，例如血管生成、肿瘤细胞浸润和原发部位的血管浸润(PubMed:28210073)。它们还调节对肿瘤的免疫反应以抑制肿瘤清除，并直接与肿瘤细胞结合以激活促存活的信号通路(PubMed:17527089)。巨噬细胞的募集、增殖和不可逆分化受集落刺激因子1(CSF-1)的调控(PubMed:28716061,PubMed:22186992)，这是一种经常在腱鞘巨细胞瘤中易位并高表达的细胞因子(PubMed:17527089)。CSF-1和CSF-1受体(CSF1R)的高表达也与多种恶性肿瘤模型有关(PubMed:19443701)。Pexidartinib作为CSF1R选择性抑制剂可靶向CSF1/CSF1R途径。它通过与CSF1R的近膜区域相互作用来刺激CSF1R的自身抑制状态，并阻止CSF1和ATP与该区域结合，其中CSF1R负责激酶结构域的折叠和失活(PubMed:30002809)。CSF1与受体不结合时，CSF1R不能进行配体诱导的自磷酸化。Pexi
Ponatinib 普纳替尼 Iclusig TakedaPharmsUSA 2012/12/14 FDA Iclusig is a kinase inhibitor indicated for the treatment of adult patients with: 1.Chronic phase (CP) chronic myeloid leukemia (CML) with resistance or intolerance to at least two prior kinase inhibitors.2.Accelerated phase (AP) or blast phase (BP) CML or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other kinase inhibitors are indicated.3.T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL. Iclusig是一种激酶抑制剂，其适应症为：1.对至少两种激酶抑制剂耐药或不耐受的慢性髓系白血病(CML)或Ph+ALL成人患者。2.不适用其他激酶抑制剂的加速期或急变期CML或费城染色体阳性急性淋巴细胞白血病(Ph+ ALL)成人患者。3.T315I阳性CML(慢性期、加速期或急变期)或T315I阳性费城染色体阳性急性淋巴细胞白血病(Ph+ ALL)成人患者。 慢性髓系白血病、急性淋巴细胞白血病 Ponatinib is a kinase inhibitor. Ponatinib inhibited the in vitro tyrosine kinase activity of ABL and T315I mutant ABL with IC50 concentrations of 0.4 nM and 2.0 nM, respectively. Ponatinib inhibited the in vitro activity of additional kinases with IC50 concentrations between 0.1 nM and 20 nM, including members of the VEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2, and FLT3. Ponatinib inhibited the in vitro viability of cells expressing native or mutant BCR-ABL, including T315I. In mice, treatment with ponatinib reduced the size of tumors expressing native or T315I mutant BCR-ABL when compared to controls. Ponatinib是一种激酶抑制剂。Ponatinib可以抑制ABL和ABL T315I突变的体外酪氨酸激酶活性，IC50浓度分别为0.4 nM和2.0 nM。Ponatinib还可以抑制一些其他激酶的体外活性，这些激酶包括VEGFR、PDGFR、FGFR、EPH受体和SRC激酶家族成员以及KIT、RET、TIE2和FLT3，其IC50浓度在0.1 nM至20 nM之间。Ponatinib能抑制表达天然或突变（包括T315I）BCR-ABL细胞的体外活力。在小鼠中，用Ponatinib治疗与对照组相比可减少表达天然或T315I突变BCR-ABL肿瘤的大小。 12/2020 2021/11/26 pj/sjz D0101
Poziotinib 波齐替尼 乳腺癌、肺腺 Poziotinib has been used in trials studying the treatment of Breast Cancer, Metastatic Breast Cancer, Increased Drug Resistance, Adenocarcinoma of Lung Stage IV, and Adenocarcinoma of Lung Stage IIIB, among others. Poziotinib已用于乳腺癌、转移性乳腺癌、耐药性增加、IV期肺腺癌和IIIB期肺腺癌治疗的研究试验中。Poziotinib （波奇替尼）特异性抑制HER2扩增的胃癌细胞生长，并抑制EGFR的磷酸化和下游信号级联放大的关键组分，比如STAT3，AKT 和ERK。Poziotinib （波奇替尼）也会通过激活HER2扩增的胃癌细胞中线粒体途径，诱导细胞凋亡和G1细胞周期阻滞。此外，在HER2诱发的和HER2非扩增的胃癌细胞中，Poziotinib （波奇替尼）与化疗剂发挥出协同作用。在负荷N87人胃癌异种移植物的裸鼠体内，Poziotinib (0.5 mg/kg p.o.)单独使用显著抑制肿瘤生长，Poziotinib （波奇替尼） 与 5-FU联合使用显示出更有效的肿瘤抑制。此外，在各种EGFR和HER-2依赖性肿瘤异种移植模型，包括erlotinib敏感的HCC827 NSCLC细胞，erlotinib耐药的NCI-H1975 NSCLC细胞，HER-2过表达的Calu-3 NSCLC细胞，NCI-N87胃癌细胞，SK-Ov3卵巢癌细胞和EGFR过表达的A431表皮样癌细胞中，Poziotinib （波奇替尼）显示出优良的抗肿瘤活性。 1.Poziotinib （波奇替尼）是一种新型口服癌细胞抑制剂，用于治疗NSCLC、乳腺癌和胃癌，且具有靶向性的酪氨酸激酶小分子抑制剂。对于吉非替尼和厄洛替尼耐药性EGFR L858R/T790M双突变细胞有很强的抑制作用。2.Poziotinib （波奇替尼）和5-氟脲嘧啶，铂化合物，紫杉醇或吉西他滨的联合使用对于2号人体表皮(HER2)的过度表达显示出很好的协同抑制效果，是继第二代酪氨酸激酶抑制剂阿法替尼之后的一种新型第三代抗肿瘤细胞抑制剂。 2021/11/26 D0102
Pralsetinib 普拉替尼 Gavreto 普吉华 基因泰克 2020/9/4 FDA/NMPA GAVRETO is a kinase inhibitor indicated for treatment of: 1.Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer. 2.Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy. 3.Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) GAVRETO是一种激酶抑制剂，其适应症为：1.转移性、转染重排(RET)基因融合阳性的非小细胞肺癌成人患者。2.需要接受系统治疗的晚期或转移性RET突变的甲状腺髓样癌(MTC)成人和儿童(≥12岁)患者。3.需要接受系统治疗，且放射性碘难治性(如果放射性碘合适)的晚期或转移性RET融合阳性的甲状腺癌成人和儿童(≥12岁)患者。2021年NMPA批准普拉替尼适用于非小细胞肺癌患者的治疗。2022年NMPA批准普拉替尼适用于甲状腺髓样癌患者的治疗。 非小细胞肺癌、甲状腺癌 Rearranged during transfection (RET) is a transmembrane receptor tyrosine kinase containing extracellular, transmembrane, and intracellular domains whose activity is required for normal kidney and nervous system development(PubMed:2992805,PubMed:32083997).Constitutive RET activation is achieved through chromosomal rearrangements producing 5' fusions of dimerizable domains to the 3'RETtyrosine kinase domain leading to constitutive dimerization and subsequent autophosphorylation; the most common fusions areKIF5B-RETandCCDC6-RET, although more than 35 genes have been reported to fuse withRET(PubMed:32083997,PubMed:32296961,PubMed:25047660).Constitutive activation leads to increased downstream signalling and is associated with tumour invasion, migration, and proliferation(PubMed:31715421).Pralsetinib (formerly referred to as BLU-667) was developed through screening more than 10,000 agnostically designed kinase inhibitors followed by extensive chemical modification to improve its properties. Pralsetinib displaysin vitroIC50values for both WT RET as well as several mutant forms, including CCDC6-RET, in the range of 0.3-0.4 nmol/L, and is 100-fold more selective for RET kinase over 96% of 371 kinases tested(PubMed:29657135).It is this specific inhibition of RET kinase that is associated with anti-tumour activity and clinical benefit in patients(PubMed:29657135,PubMed:30257958).Despite increased selectivity for RET over other kinases, pralsetinib has been reported to inhibit DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1-2 at clinically relevant concentrations. The significance of these findings remains uncertain. 转染期间重排（RET）是一种跨膜受体酪氨酸激酶，由胞外区、跨膜区和胞内结构域组成，其活性是肾脏和神经系统正常发育所必需的（PubMed: 2992805，PubMed: 32083997）。RET组成性激活是通过染色体重排实现的，该重排导致可二聚结构域5'端与RET酪氨酸激酶结构域3'端发生融合，从而导致组成性二聚化和随后的自磷酸化。目前据报道已有超过35个基因可与RET发生融合，其中最常见的融合形式是KIF5B-RET和CCDC6-RET（PubMed: 32083997，PubMed: 32296961，PubMed: 25047660）。组成性激活导致下游信号传导增强，并与肿瘤的侵袭、迁移和增殖有关（PubMed: 31715421）。普拉替尼（Pralsetinib，以前称为BLU-667）是从10000多种候选激酶抑制剂中进行筛选，然后进行广泛的化学修饰以改善其效力而开发出的药物。普拉替尼（Pralsetinib）对WT RET以及包括CCDC6-RET在内的几种突变的体外IC50值在0.3-0.4 nmol/L之间，在包含371种激酶的激酶库中，对RET的选择性比对其中96%的激酶选择性高100倍（PubMed: 29657135）。正是由于这种对RET激酶的特异性抑制作用使得该药具有抗<E69C89>
Quizartinib 奎扎替尼 Vanflyta 第一三共株式会社 2019/10/10 MHLW 急性髓系白血病 Quizartinib potently inhibits FLT3, a kinase that is mutated in approximately one-third of acute myeloid leukemia cases, and patients with FLT3 mutations are less responsive to traditional therapies. 奎扎替尼（Quizartinib）可有效抑制FLT3活性，该激酶在近1/3的急性髓性白血病患者中发生突变，并且具有FLT3突变的患者对传统疗法的反应较差。 Quizartinib(奎扎替尼) 属于第二代FLT3抑制剂，该药是一种口服小分子受体酪氨酸激酶抑制剂，选择性靶向抑制FLT3。Quizartinib在美国获FDA授予治疗复发性/难治性FLT3-ITD AML成人患者的突破性药物资格、治疗复发性/难治性AML的快速通道地位。Quizartinib在美国、欧盟均被授予了治疗AML的孤儿药资格。Quizartinib在日本被授予了治疗FLT3突变AML的孤儿药资格。2019年6月，Vanflyt获得日本卫生劳动福利部（MHLW）批准，这是该药在全球范围内的首个监管批准。2019年10月10日，日本药企第一三共制药（Daiichi Sankyo）宣布，在日本推出口服FLT3抑制。Vanflyta（quizartinib），该药用于治疗复发性/难治性FLT3-ITD急性髓性白血病（AML）成人患者。目前，Vanflyta也正在接受欧洲药品管理局（EMA）的加速评估。 2021/11/26 pj/sjz D0105
Ramucirumab 雷莫西尤单抗 Cyramza 希冉择 Eli Lilly and Company 2014/4/21 0:00 FDA/NMPA CYRAMZA is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist indicated: 1. as a single agent or in combination with paclitaxel, for treatment of advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. 2.in combination with erlotinib, for first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations. 3.in combination with docetaxel, for treatment of metastatic nonsmall cell lung cancer with disease progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression onFDA-approved therapy for these aberrations prior to receiving CYRAMZA. 4.in combination with FOLFIRI, for the treatment of metastatic colorectal cancer with disease progression on or after priortherapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. 5. as a single agent, for the treatment of hepatocellular carcinoma in patients who have an alpha fetoprotein of ≥400 ng/mL and have been treated with sorafenib. CYRAMZA是一种人血管内皮生长因子受体2(VEGFR2)拮抗剂，其适应症为：1.单药或联合紫杉醇用于治疗既往接受含氟嘧啶或铂化疗期间或之后疾病进展的晚期或转移性胃癌或食管胃交界处腺癌。2.联合厄洛替尼用于一线治疗携带表皮生长因子受体(EGFR)19号外显子缺失或21号外显子(L858R)突变的转移性非小细胞肺癌。3.联合多西他赛用于治疗铂类化疗期间或之后疾病进展的转移性非小细胞肺癌。4.联合FOLFIRI方案用于治疗既往接受贝伐单抗、奥沙利铂和氟嘧啶治疗期间或之后疾病进展的转移性结直肠癌。5.单药用于治疗甲胎蛋白≥400 ng/mL且既往接受过索拉非尼治疗的肝细胞癌患者。NMPA批准雷莫西尤单抗联合紫杉醇用于在含氟尿嘧啶类或含铂类化疗期间或化疗后出现疾病进展的晚期胃或胃食管结合部腺癌患者的治疗；2022年NMPA批准雷莫西尤单抗作为单药用于既往接受过索拉非尼治疗且甲胎蛋白≥400ng/mL 的肝细胞癌患者的治疗。 胃癌、食管胃交界处腺癌、非小细胞肺癌、结直肠癌、肝细胞癌 Ramucirumab is a VEGFR2 antagonist that specifically binds VEGFR2 and blocks binding of VEGFR ligands, VEGF-A,VEGF-C, and VEGF-D. As a result, ramucirumab inhibits ligand-stimulated activation of VEGFR2, thereby inhibitingligand-induced proliferation, and migration of human endothelial cells. Ramucirumab inhibited angiogenesis in an in vivoanimal model. Ramucirumab是一种VEGFR2拮抗剂，能特异性结合VEGFR2并阻断VEGFR配体VEGF-A、VEGF-C、VEGF-D的结合。因此，雷莫卢单抗(Ramucirumab)可以抑制配体刺激的VEGFR2激活，进而抑制配体诱导的人内皮细胞增殖和迁移。雷莫卢单抗(Ramucirumab)在体内动物模型中可以抑制血管的生成。 06/2021 2023/5/26 0:00 sxz D0106 批准单位与名称修改 LXL
Regorafenib 瑞戈非尼 Stivarga 拜万戈 拜耳医药 2012/9/27 FDA/NMPA STIVARGA is a kinase inhibitor indicated for the treatment of patients with:1.Metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy.2.Locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.3. Hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. STIVARGA是一种激酶抑制剂，其适应症为：1.既往接受过氟嘧啶、奥沙利铂和伊立替康为基础化疗、抗VEGF治疗、以及抗EGFR治疗(如果是RAS野生型时)的转移性结直肠癌(CRC)。2.既往接受过甲磺酸伊马替尼和苹果酸舒尼替尼治疗的局部晚期、不可切除性或转移性胃肠道间质瘤(GIST)。3.既往接受过索拉非尼治疗的肝细胞癌(HCC)。2017年NMPA批准瑞戈非尼适用结直肠癌（mCRC）患者或胃肠道间质瘤（GIST）患者的治疗。 结直肠癌、胃肠道间质瘤、肝细胞癌 Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, metastasis and tumor immunity. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA,Eph2A, RAF-1, BRAF, BRAF V600E, SAPK2, PTK5, Abl and CSF1R at concentrations of regorafenib that have been achieved clinically. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model and inhibition of tumor growth in several mouse xenograft models including some for human colorectal carcinoma, gastrointestinal stromal and hepatocellular carcinoma. Regorafenib also demonstrated anti-metastatic activity in a mouse xenograft model and two mouse orthotopic models of human colorectal carcinoma. 瑞戈非尼（Regorafenib）是一种小分子抑制剂，靶向多种与细胞膜结合的激酶以及细胞内激酶，这些激酶参与正常的细胞功能和病理过程，例如肿瘤发生、肿瘤血管生成、转移和肿瘤免疫。在体外生化或细胞试验中，瑞戈非尼（Regorafenib）或其主要人类活性代谢产物M-2和M-5可在临床浓度下抑制RET、VEGFR1、VEGFR2、VEGFR3、KIT、PDGFR-α、PDGFR-β、FGFR1、FGFR2、TIE2、DDR2、TrkA、Eph2A、RAF-1、BRAF、BRAF V600E、SAPK2、PTK5、Abl和CSF1R的活性。瑞戈非尼（Regorafenib）在大鼠体内肿瘤模型中显示出抗血管生成活性，并在几种小鼠异种移植瘤模型（包括某些人结直肠癌、胃肠道间质癌和肝细胞癌）中显示出对肿瘤生长的抑制作用。瑞戈非尼（Regorafenib）还在小鼠异种移植模型和人结直肠癌的两个小鼠原位模型中证实了抗转移活性。 FDA-approval:12/2020;NMPA-approval:2017 2023/6/20 sxz D0107
Ripretinib 瑞派替尼 Qinlock 擎乐 Deciphera医药 2020/5/15 0:00 FDA/NMPA QINLOCK is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. QINLOCK是一种激酶抑制剂，适用于既往接受过3种或更多激酶抑制剂(包括伊马替尼)治疗的晚期胃肠道间质瘤(GIST)成人患者。2021年NMPA批准瑞派替尼适用于既往接受过3种或以上酪氨酸激酶抑制剂（包括伊马替尼）的晚期胃肠间质瘤（GIST）成人患者的治疗。 胃肠道间质瘤 Protein kinases play important roles in cellular function, and their dysregulation can lead to carcinogenesis(PubMed:30259761).Ripretinib inhibits protein kinases including wild type and mutant platelet-derived growth factor receptor A (PDGFRA) and KIT that cause the majority of gastrointestinal stromal tumor (GIST)(PubMed:32273716).In vitro, ripretinib has been shown to inhibit PDGFRB, BRAF, VEGF, and TIE2 genes(PubMed:31205499,PubMed:31267077).Ripretinib binds to KIT and PDGFRA receptors with mutations on the exons 9, 11, 13, 14, 17 and 18 (for KIT mutations), and exons 12, 14 and 18 (for PDGFRA mutations)(PubMed:31755321).The “switch pocket” of a protein kinase is normally bound to the activation loop, acting as an “on-off switch” of a kinase. Ripretinib boasts a unique dual mechanism of action of binding to the kinase switch pocket as well as the activation loop, thereby turning off the kinase and its ability to cause dysregulated cell growth(PubMed:31755321). 蛋白激酶在细胞功能中起重要作用，其功能失调可导致肿瘤的发生（PubMed: 30259761）。瑞派替尼（Ripretinib）可抑制包括野生型和突变型血小板衍生生长因子受体A（PDGFRA）和KIT在内的多种蛋白激酶活性，其中PDGFRA和KIT突变可引发大多数胃肠道间质瘤（GIST）（PubMed: 32273716）。瑞派替尼（Ripretinib）在体外可抑制其他激酶，如PDGFRB、BRAF、VEGF和TIE2基因（PubMed: 31205499，PubMed: 31267077）。瑞派替尼（Ripretinib）能与KIT第9、11、13、14、17和18号外显子突变和PDGFRA第12、14和18号外显子突变的受体结合（PubMed: 31755321）。蛋白激酶的“开关口袋”通常与激活环相连，充当激酶活性的“开关”。瑞派替尼（Ripretinib）拥有独特的双重作用机制，结合激酶开关口袋和激活环，从而关闭激酶，并使其丧失导致细胞生长失调的能力（PubMed: 31755321）。 FDA-approval: 06/2021;NMPA-approval: 2021 231218 pj D0109 作用机制中的药物名称订正 SXZ
Rucaparib 芦卡帕尼 Rubraca Clovis Oncology, Inc 2016-12-19 00:00:00 FDA RUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:Ovarian cancer• for the maintenance treatment of adult patients with a deleterious BRCAmutation (germline and/or somatic)- associated recurrent epithelial ovarian,fallopian tube, or primary peritoneal cancer who are in a complete or partialresponse to platinum-based chemotherapy. Prostate cancer• for the treatment of adult patients with a deleterious BRCA mutation(germline and/or somatic)-associated metastatic castration-resistant prostatecancer (mCRPC) who have been treated with androgen receptor-directedtherapy and a taxane-based chemotherapy. RUBRACA是一种聚(ADP-核糖)聚合酶(PARP)抑制剂，其适应症包括：1.卵巢癌：用于携带有害BRCA突变(胚系和/或体细胞)相关的复发性上皮性卵巢癌、输卵管癌或原发性腹膜癌成人患者在含铂化疗达到完全或部分缓解后的维持治疗。2.前列腺癌：用于治疗携带有害BRCA突变(胚系和/或体细胞)相关的转移性去势抵抗性前列腺癌(mCRPC)成人患者，这些患者既往接受过雄激素受体靶向治疗和含紫杉醇类化疗。 卵巢癌、输卵管癌、原发性腹膜癌、前列腺癌 Rucaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP-1, PARP-2, and PARP-3, which play a role in DNA repair. In vitro studies have shown that rucaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cancer cell death. Increased rucaparib-induced cytotoxicity and anti-tumor activity was observed in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes. Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA. Rucaparib是聚（ADP-核糖）聚合酶（PARP）抑制剂，包括PARP1、PARP2和PARP3，它们在DNA修复中起作用。体外研究表明，Rucaparib诱导的细胞毒性可能涉及PARP酶活性抑制和PARP-DNA复合物形成增加，从而导致DNA损伤、凋亡和细胞死亡。在BRCA1/2和其他DNA修复基因缺陷的肿瘤细胞系中可观察到Rucaparib诱导的细胞毒性和抗肿瘤活性的增加。在有或无BRCA缺陷的人源肿瘤小鼠异种移植模型中，Rucaparib可降低肿瘤的生长。 12/2022 230714 pj D0112 适应症修改 LXL
Ruxolitinib 芦可替尼 Jakafi 捷恪卫 Novartis Pharma Schweiz AG 2011/11/16 0:00 FDA/NMPA Jakafi is a kinase inhibitor indicated for treatment of:1.intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis in adults. 2.polycythemia vera in adults who have had an inadequate response to or are intolerant of hydroxyurea.3. steroid-refractory acute graft-versus-host disease in adult and pediatric patients 12 years and older.4.chronic graft-versus-host disease after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. Jakafi是一种激酶抑制剂，其适应症为：1.中度或高危骨髓纤维化，包括成人原发性骨髓纤维化、真性红细胞增多症后骨髓纤维化和原发性血小板增多症后骨髓纤维化。2 .对羟基脲反应不足或不能耐受的成人真性红细胞增多症。3.类固醇难治性急性移植物抗宿主病成人和儿童(≥12岁)患者。4.1或2种系统治疗失败的慢性移植物抗宿主病成人和儿童(≥12岁)患者。2021年NMPA批准用于中危或高危的原发性骨髓纤维化（PMF）（亦称为慢性特发性骨髓纤维化）、真性红细胞增多症继发的骨髓纤维化（PPV-MF）或原发性血小板增多症继发的骨髓纤维化（PET-MF）的成年患者，治疗疾病相关脾肿大或疾病相关症状。 骨髓纤维化，真性红细胞增多症，移植物抗宿主病 Ruxolitinib, a kinase inhibitor, inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2 which mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression.MF and PV are myeloproliferative neoplasms (MPN) known to be associated with dysregulated JAK1 and JAK2 signaling. In a mouse model of JAK2V617F-positive MPN, oral administration of ruxolitinib prevented splenomegaly, preferentially decreased JAK2V617F mutant cells in the spleen and decreased circulating inflammatory cytokines (e.g., TNF-α, IL-6).JAK-STAT signaling pathways play a role in regulating the development, proliferation, and activation of several immune cell types important for GVHD pathogenesis. In a mouse model of aGVHD, oral administration of ruxolitinib was associated with decreased expression of inflammatory cytokines in colon homogenates and reduced immune-cell infiltration in the colon. 芦可替尼（Ruxolitinib)是一种Janus相关激酶（JAK）1和2的选择性激酶抑制剂。这些激酶负责介导细胞因子和生长因子信号传导，进而影响免疫功能和造血功能。信号转导过程包含调控基因表达的信号转导子和转录激活子（STAT）。骨髓纤维化患者的JAK1和JAK2活性异常，因此芦可替尼（Ruxolitinib)可用以调节。 09/2021 2023/5/26 0:00 SXZ D0113 批准单位与名称修改 LXL非恶性肿瘤
Selpercatinib 塞普替尼 Retevmo 睿妥 Loxo Oncology, Inc 2020/5/8 FDA/NMPA RETEVMO is a kinase inhibitor indicated for the treatment of:1. Adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC). 2.Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy. 3.Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).4. Adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. RETEVMO是一种激酶抑制剂，其适应症为：1.转移性RET融合阳性非小细胞肺癌(NSCLC)成人患者。2.需要系统治疗的晚期或转移性RET突变型甲状腺髓样癌(MTC)成人和儿童(≥12岁)患者。3.需要系统治疗且放射性碘难治性(如果需要放射性碘)的晚期或转移性RET融合阳性甲状腺癌成人和儿童(≥12岁)患者。4.携带RET融合的转移性实体瘤患者，且在之前的系统性治疗后疾病进展，或者没有令人满意的治疗替代方案。2022年NMPA批准塞普替尼适用于非小细胞肺癌,甲状腺癌,甲状腺髓样癌和实体瘤患者。 非小细胞肺癌、甲状腺癌、实体瘤 Selpercatinib is a kinase inhibitor. Selpercatinib inhibited wild-type RET and multiple mutated RET isoforms as well as VEGFR1 and VEGFR3 with IC50 values ranging from 0.92 nM to 67.8 nM. In other enzyme assays, selpercatinib also inhibited FGFR 1, 2, and 3 at higher concentrations that were still clinically achievable. In cellular assays, selpercatinib inhibited RET at approximately 60-fold lower concentrations than FGFR1 and 2 and approximately 8-fold lower concentration than VEGFR3.Certain point mutations in RET or chromosomal rearrangements involving in-frame fusions of RET with various partners can result in constitutively activated chimeric RET fusion proteins that can act as oncogenic drivers by promoting cell proliferation of tumor cell lines. In in vitro and in vivo tumor models, selpercatinib demonstrated anti-tumor activity in cells harboring constitutive activation of RET protein resulting from gene fusions and mutations, including CCDC6-RET, KIF5B-RET, RET V804M, and RET M918T. In addition, selpercatinib showed anti-tumor activity in mice intracranially implanted with a patient-derived RET fusion positive tumor. Selpercatinib是一种激酶抑制剂。Selpercatinib可抑制野生型RET和多种突变的RET亚型以及VEGFR1和VEGFR3，IC50值在0.92 nM至67.8 nM之间。在其他酶分析中，Selpercatinib还可以在临床上仍可达到的更高浓度下抑制FGFR1、2和3的活性。在细胞试验中，Selperctinib抑制RET的浓度比FGFR1和2低约60倍，比VEGFR3低约8倍。RET的某些点突变或RET与各种伴侣基因框内融合导致的染色体重排可产生组成性激活的嵌合RET融合蛋白，其可充当致癌驱动因子，促进肿瘤细胞系的增殖。在体外试验和体内肿瘤模型中，Selperctinib在由基因融合和突变（包括CCDC6-RET、KIF5B-RET、RET V804M和RET M918T）产生的RET蛋白组成性激活细胞中表现出抗肿瘤活性。此外，Selperctinib在颅内移植患者源性RET融合阳性肿瘤的小鼠中也显示出抗肿瘤活性。 FDA-approval:01/2021 2023/6/20 sxz D0115 批准单位及适应证修改
Selumetinib 司美替尼 Koselugo 科赛优 AstraZeneca 2020/4/10 0:00 FDA/NMPA KOSELUGO is a kinase inhibitor indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). KOSELUGO是一种激酶抑制剂，适用于2岁及以上患有1型神经纤维瘤(NF1)、有症状的、不能手术的丛状神经纤维瘤(PN)的儿童患者。 神经纤维瘤 Selumetinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers.In genetically modified mouse models of NF1 that generate neurofibromas that recapitulate the genotype and phenotype of human NF1, oral dosing of selumetinib inhibited ERK phosphorylation, and reduced neurofibroma numbers, volume, and proliferation. Selumetinib是丝裂原活化蛋白激酶激酶1和2（MEK1/2）的抑制剂。MEK1/2蛋白是细胞外信号相关激酶（ERK）途径的上游调节因子。MEK和ERK都是RAS调节的RAF-MEK-ERK通路的关键组成部分，该通路通常在不同类型的癌症中被激活。在产生与人类NF1基因型和表型相似的神经纤维瘤的转基因NF1小鼠模型中，口服塞洛替尼抑制ERK磷酸化，并减少神经纤维瘤的数量、体积和增殖。 04/2020 2023/5/26 0:00 SXZ D0116 批准单位与名称修改 LXL
Sirolimus 西罗莫司 Pfizer Ireland Pharmaceuticals 2000/8/25 FDA/NMPA Rapamune is an mTOR inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in patients aged ≥13 years receiving renal transplants: 1.Patients at low- to moderate-immunologic risk: （1）Use initially with cyclosporine (CsA) and corticosteroids. CsA withdrawal is recommended 2-4 months after transplantation.（2）.Patients at high-immunologic risk: Use in combination with CsA and corticosteroids for the first 12 months following transplantation.2.Rapamune is an mTOR inhibitor indicated for the treatment of patients with lymphangioleiomyomatosis. Rapamune是一种mTOR抑制剂免疫抑制剂，用于预防以下接受肾移植的年龄≥13岁的患者的器官排斥反应：(1)低至中度免疫风险患者：最初使用环孢菌素（CsA）和皮质类固醇。移植后2-4个月推荐CsA戒断。(2)高免疫风险的患者：在移植后的前12个月与CsA和皮质类固醇联合使用。2.Rapamune是一种mTOR抑制剂，用于治疗淋巴管平滑肌瘤病患者。2007年NMPA批准西罗莫司适用于肾移植患者。 淋巴管平滑肌瘤 Sirolimus inhibits T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (Interleukin IL-2, IL-4, and IL-15) stimulation by a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus:FKBP-12 complex has no effect on calcineurin activity. This complex binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This inhibition suppresses cytokine-driven T-cell proliferation, inhibiting the progression from the G1 to the S phase of the cell cycle. 西罗莫司(Sirolimus)通过抑制抗原和细胞因子(白介素IL-2、IL-4和IL-15)激发的T淋巴细胞的活化和增殖。西罗莫司(Sirolimus)亦抑制抗体的产生。在细胞中，西罗莫司(Sirolimus)与亲免蛋白，即FK结合蛋白-12(FKBP-12)结合，生成一个免疫抑制复合物。该复合物对钙调神经磷酸酶的活性没有影响。此复合物与哺乳动物雷帕霉素靶蛋白(mTOR，一种关键的调节激酶)结合并抑制其活性。这种抑制作用阻遏了细胞因子驱动的T细胞增殖，即抑制细胞周期从G1期向S期的过渡。 FDA-approval:08/2021;NMPA-approval:2007 2023/6/20 sxz D0117
Sonidegib 索立德吉 Odomzo 奥昔朵 Patheon Inc. 2015/7/24 0:00 FDA/NMPA ODOMZO is a hedgehog pathway inhibitor indicated for the treatment of adult patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. ODOMZO是一种Hedgehong通路抑制剂，适用于手术或放疗后复发、或不适合手术或放疗的局部晚期基底细胞癌(BCC)成人患者。 基底细胞癌 Sonidegib is an inhibitor of the Hh pathway. Sonidegib binds to and inhibits Smoothened, a transmembrane protein involved in Hh signal transduction. Sonidegib是一种Hh通路抑制剂。Sonidegib可结合并抑制Smoothened活性，后者作为一种跨膜蛋白参与Hh信号传导。 05/2019 2023/5/26 0:00 SXZ D0118 批准单位与名称修改 LXL
Sorafenib 索拉非尼 Nexavar 多吉美 拜耳医药 2005/12/1 FDA/NMPA NEXAVAR is a kinase inhibitor indicated for the treatment of：1.Unresectable hepatocellular carcinoma. 2.Advanced renal cell carcinoma. 3. Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment. Sorafenib是一种激酶抑制剂，其适应症为：1.不可切除的肝细胞癌。2.晚期肾细胞癌。3.对放射性碘治疗无效的局部复发或转移性、进行性、分化型甲状腺癌(DTC)。2006年NMPA批准索拉非尼适用于肾细胞癌，肝细胞癌和甲状腺癌。 肝癌，肾癌，甲状腺癌 Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro. Sorafenib was shown to inhibit multiple intracellular (c-CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT- 3, RET, RET/PTC, VEGFR-1, VEGFR- 2, VEGFR- 3, and PDGFR-). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis and apoptosis. Sorafenib inhibited tumor growth of HCC, RCC, and DTC human tumor xenografts in immunocompromised mice. Reductions in tumor angiogenesis were seen in models of HCC and RCC upon sorafenib treatment, and increases in tumor apoptosis were observed in models of HCC, RCC, and DTC. 索拉非尼是一种激酶抑制剂，可在体外降低肿瘤细胞增殖。索拉非尼可抑制多种细胞内（c-CRAF、BRAF和突变BRAF）和细胞表面激酶（KIT、FLT-3、RET、RET/PTC、VEGFR-1、VEGFR-2、VEGFR-3和PDGFR-）的活性。其中一些激酶被认为与肿瘤细胞信号传导、血管生成和凋亡有关。索拉非尼抑制免疫功能低下小鼠中HCC、RCC和DTC人源肿瘤异种移植物的肿瘤生长。索拉非尼治疗后，HCC和RCC模型的肿瘤血管生成减少，HCC、RCC和DTC模型的肿瘤凋亡增加。 FDA-approval:07/2020;NMPA-approval:2018 索拉非尼（Sorafenib）与多种细胞内（CRAF、BRAF和突变型BRAF）和细胞表面激酶（KIT、FLT-3、VEGFR-2、VEGFR-3和PDGFR-）相互作用。这些激酶中有几种与血管生成有关，因此索拉非尼（Sorafenib）减少了肿瘤的血液供应。索拉非尼（Sorafenib）可独特靶向Raf/Mek/Erk途径。通过抑制这些激酶的活性，涉及细胞增殖和血管生成的基因转录受到抑制。 2023/6/20 sxz D0119 修改日期；sxz
Sotorasib 索托拉西布 Lumakras Amgen Inc 2021/5/28 FDA LUMAKRAS is an inhibitor of the RAS GTPase family indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), who have received at least one prior systemic therapy. Sotorasib是一种RAS GTP酶家族蛋白抑制剂，适用于既往接受过至少一种全身治疗方案的携带KRAS G12C突变的局部晚期或转移性非小细胞肺癌成人患者。 非小细胞肺癌 Sotorasib is an inhibitor of KRASG12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRASG12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines. Sotorasib inhibited KRASG12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models sotorasib-treatment led to tumor regressions and prolonged survival and was associated with anti-tumor immunity in KRAS G12C models. Sotorasib是KRAS G12C的抑制剂，G12C突变是KRAS基因的一种致癌突变，Sotorasib和G12C独特的半胱氨酸形成不可逆的共价键，将突变的KRAS蛋白处于非激活状态，从而抑制下游促癌信号通路的传导，且不影响野生型KRAS的功能。 05/2021 2021/11/26 pj/sjz D0120
Sunitinib 舒尼替尼 Sutent 索坦 Pfizer Italia S.R.I 2006/1/26 FDA/NMPA SUTENT is a kinase inhibitor indicated for: 1.treatment of adult patients with gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate. 2.treatment of adult patients with advanced renal cell carcinoma (RCC). 3.adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy. 4.treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in adult patients with unresectable locally advanced or metastatic disease. SUTENT是一种激酶抑制剂，其适应症为：1.甲磺酸伊马替尼治疗失败或不能耐受的胃肠间质瘤(GIST)成人患者。2.晚期肾细胞癌(RCC)成人患者。3.肾切除术后存在高复发风险的肾细胞癌成人患者的辅助治疗。4.不可切除的局部晚期或转移性的高分化进展期胰腺神经内分泌肿瘤(pNET)成人患者。2007年舒尼替尼首次获得NMPA批准，至2015年NMPA批准其适用于胃肠道间质瘤，肾细胞癌和胰腺神经内分泌肿瘤。 胃肠间质瘤、肾细胞癌、腺神经内分泌肿瘤 Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.Sunitinib inhibited the phosphorylation of multiple RTKs (PDGFRβ, VEGFR2, KIT) in tumor xenografts expressing RTK targets in vivo and demonstrated inhibition of tumor growth or tumor regression and/or inhibited metastases in some experimental models of cancer. Sunitinib demonstrated the ability to inhibit growth of tumor cells expressing dysregulated target RTKs (PDGFR, RET, or KIT) in vitro and to inhibit PDGFRβ- and VEGFR2-dependent tumor angiogenesis in vivo. 舒尼替尼（Sunitinib）是多种受体酪氨酸激酶(RTK)的小分子抑制剂，其中某些激酶与肿瘤的生长、病理性血管生成和肿瘤转移有关。舒尼替尼（Sunitinib）对多种激酶（> 80种激酶）的抑制活性已得到评价，已确定为以下受体的抑制剂：血小板衍生生长因子受体（PDGFRa和PDGFRb）、血管内皮生长因子受体（VEGFR1、VEGFR2和VEGFR3）、干细胞因子受体（KIT）、Fms样酪氨酸激酶3（FLT3）、集落刺激因子-1受体（CSF-1R）以及胶质细胞源性神经营养因子受体（RET）。生化和细胞试验证实舒尼替尼（Sunitinib）能抑制这些受体酪氨酸激酶（RTK）的活性，并且在细胞增殖试验中证明了舒尼替尼（Sunitinib）的抑制作用。生化和细胞试验表明舒尼替尼（Sunitinib）主要代谢物的活性与其相似。舒尼替尼（Sunitinib）在体内表达RTK的肿瘤异种移植物中可抑制多种 RTK（PDGFRβ、VEGFR2、KIT）磷酸化，并且在某些肿瘤实验模型中显示出抑制肿瘤生长或肿瘤消退和/或抑制转移。舒尼替尼（Sunitinib）在体外能够抑制表达失调RTK（PDGFR、RET或KIT）的肿瘤细胞的生长，并在体内抑制PDGFRβ和VEGFR2依赖性肿瘤血管生成。 FDA-approval:08/2021;NMPA-approval:2015 2023/6/20 sxz D0121
Talazoparib 他拉唑帕尼 Talzenna 辉瑞 2018-10-16 00:00:00 FDA TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicatedfor:Breast Cancer• As a single agent, for the treatment of adult patients with deleterious orsuspected deleterious germline BRCA-mutated (gBRCAm) HER2-negativelocally advanced or metastatic breast cancer. Select patients for therapybased on an FDA-approved companion diagnostic for TALZENNA. HRR Gene-mutated mCRPC• In combination with enzalutamide for the treatment of adult patients withHRR gene-mutated metastatic castration-resistant prostate cancer(mCRPC). TALZENNA是一种多（ADP核糖）聚合酶（PARP）抑制剂，其适应症包括：1.乳腺癌：单药用于治疗携带有害或疑似有害胚系BRCA突变（gBRCAm）、HER2阴性的局部晚期或转移性乳腺癌成人患者。2.HRR基因突变的mCRPC：联合恩扎卢胺用于治疗HRR基因突变的转移性去势抵抗性前列腺癌（mCRPC）成人患者。 乳腺癌、前列腺癌 Talazoparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2,which play a role in DNA repair. In vitro studies with cancer cell lines that harbored defects in DNA repairgenes, including BRCA1 and BRCA2, have shown that talazoparib-induced cytotoxicity may involve inhibitionof PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage,decreased cell proliferation, and apoptosis. Talazoparib anti-tumor activity was observed in patient-derivedxenograft breast cancer models bearing mutated BRCA1 or mutated BRCA2 or wild type BRCA1 and BRCA2. 他拉唑帕尼（Talazoparib）是多（ADP-核糖）聚合酶（PARP）的抑制剂，包括在DNA修复中发挥作用的PARP1和PARP2。对DNA修复基因（包括BRCA1和BRCA2）存在缺陷的癌细胞系进行的体外研究表明，talazoparib诱导的细胞毒性可能涉及抑制PARP酶活性和增加PARP-DNA复合物的形成，从而导致DNA损伤、细胞增殖减少和凋亡。Talazoparib的抗肿瘤活性可在携带BRCA1/2突变或野生型BRCA1/2的患者来源异种移植乳腺癌模型中观察到。 06/2023 230714 pj D0122 适应症修改 LXL
Tazemetostat Tazverik Epizyme Inc 2020/1/23 FDA TAZVERIK is a methyltransferase inhibitor indicated for the treatment of: 1. Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. 2.Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies. 3.Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options. TAZVERIK是一种甲基转移酶抑制剂，其适应症为：1.不符合完全切除手术条件的转移性或局部晚期上皮样肉瘤成人和儿童(≥16岁)患者。2.EZH2突变阳性、且至少接受过2次系统治疗的复发性或难治性滤泡性淋巴瘤成人患者。3.没有令人满意的替代治疗方案的复发性或难治性滤泡性淋巴瘤成人患者。 上皮样肉瘤、滤泡性淋巴瘤 EZH2 is a methyltransferase subunit of the polycomb repressive complex 2 (PRC2) which catalyzes multiple methylations of lysine 27 on histone H3 (H3K27).Trimethylation of this lysine inhibits the transcription of genes associated with cell cycle arrest(PubMed:29650364).PRC2 is antagonized by the switch/sucrose non-fermentable (SWI/SNF) multiprotein complex(PubMed:29650364).Abnormal activation of EZH2 or loss of function mutations in SWI/SNF lead to hyper-trimethylation of H3K27(PubMed:29650364).Hyper-trimethylation of H3K27 leads to cancer cell de-differentiation(PubMed:31970877).a gain of cancer stem cell-like properties(PubMed:24531722).De-differentiation can allow for cancer cell proliferation(PubMed:31970877,PubMed:24531722,PubMed:29650364).Tazemetostat inhibits EZH2preventing hyper-trimethylation of H3K27 and an uncontrollable cell cycle(PubMed:29650364). EZH2是多梳抑制复合物2（PRC2）的甲基转移酶亚基，可催化组蛋白H3的27位赖氨酸（H3K27）多甲基化。赖氨酸的三甲基化可使与细胞周期停滞相关的基因转录受到抑制（PubMed: 29650364）。交配型转换/蔗糖不发酵（SWI/SNF）多蛋白复合物可拮抗PRC2活性（PubMed: 29650364）。EZH2的异常激活或SWI/SNF功能丧失型突变可导致H3K27过度三甲基化（PubMed: 29650364）。H3K27的过度三甲基化可导致肿瘤细胞去分化（PubMed: 31970877），使肿瘤细胞获得干细胞样特性（PubMed: 24531722）。去分化可以促使肿瘤细胞增殖（PubMed: 31970877，PubMed: 24531722，PubMed: 29650364）。Tazemetostat能够抑制EZH2活性，阻止H3K27过度三甲基化以及不受控的细胞周期（PubMed: 29650364）。 06/2020 2021/11/26 D0124
Temsirolimus 坦罗莫司 Torisel Accord Healthcare 2007/5/30 FDA TORISEL is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. TORISEL是一种激酶抑制剂，适用于晚期肾细胞癌的治疗。 肾细胞癌 Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTOR that controls cell division. Inhibition of mTOR activity resulted in a Gl growth arrest in treated tumor cells. When mTOR was inhibited, its ability to phosphorylate p70S6k and S6 ribosomal protein, which are downstream of mTOR in the PI3 kinase/AKT pathway was blocked. In in vitro studies using renal cell carcinoma cell lines, temsirolimus inhibited the activity of mTOR and resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha, and the vascular endothelial growth factor. 坦罗莫司(Temsirolimus)是一种哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂。坦罗莫司(Temsirolimus)可以与细胞内蛋白(FKBP-12)结合，且该蛋白-药物复合物可抑制控制细胞分裂的mTOR活性。mTOR活性抑制会导致治疗的肿瘤细胞周期停滞在G1期。当mTOR被抑制时，其磷酸化PI3激酶/AKT途径中mTOR下游分子p70S6k和S6核糖体蛋白的能力被阻断。在使用肾细胞癌细胞系的体外研究中，坦罗莫司(Temsirolimus)可以抑制mTOR的活性并导致低氧诱导因子HIF-1和HIF-2α以及血管内皮生长因子的水平降低。 03/2018 2021/11/26 D0125
Tepotinib 特普替尼 Tepmetko 默克雪兰诺 2021/2/3 FDA TEPMETKO is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymalepithelial transition (MET) exon 14 skipping alterations. TEPMETKO是一种激酶抑制剂，适用于携带MET 14号外显子跳跃突变的转移性非小细胞肺癌成人患者。 非小细胞肺癌 Tepotinib is a kinase inhibitor that targets MET, including variants with exon 14 skipping alterations.Tepotinib inhibits hepatocyte growth factor (HGF)-dependent and -independent MET phosphorylationand MET-dependent downstream signaling pathways. Tepotinib also inhibited melatonin 2 andimidazoline 1 receptors at clinically achievable concentrations.In vitro, tepotinib inhibited tumor cell proliferation, anchorage-independent growth, and migration ofMET-dependent tumor cells. In mice implanted with tumor cell lines with oncogenic activation of MET,including METex14 skipping alterations, tepotinib inhibited tumor growth, led to sustained inhibition ofMET phosphorylation, and, in one model, decreased the formation of metastases. Tepotinib是一种靶向MET（包括14号外显子跳跃突变）的激酶抑制剂。Tepotinib可抑制肝细胞生长因子（HGF）依赖性和非依赖性MET磷酸化以及依赖MET的下游信号通路。Tepotinib还可以在临床可达到的浓度下抑制褪黑素2和咪唑啉1型受体。在体外，Tepotinib可以抑制肿瘤细胞增殖、锚定非依赖性生长和MET依赖性肿瘤细胞的迁移。在植入具有MET致癌活性肿瘤细胞系(包括MET 14号外显子跳跃突变)的小鼠中，Tepotinib抑制了肿瘤的生长，导致MET磷酸化的持续抑制，并且在一个模型中，降低了转移的形成。 02/2021 2021/11/26 D0126
Tipifarnib 替吡法尼 R115777, a nonpeptidomimetic farnesyl transferase inhibitor, The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras protein, which is commonly abnormally active in cancer. After translation, RAS goes through four steps of modification: isoprenylation, proteolysis, methylation and palmitoylation. Isoprenylation involves the enzyme farnesyltransferase (FTase) transferring a farnesyl group from farnesyl pyrophosphate (FPP) to the pre-RAS protein. Also, a related enzyme geranylgeranyltransferase I (GGTase I) has the ability to transfer a geranylgeranyl group to K and N-RAS. Farnesyl is necessary to attach RAS to the cell membrane. Without attachment to the cell membrane, RAS is not able to transfer signals from membrane receptors (Reuter et al., 2000). Tipifarnib (替吡法尼; IND 58359; R115777) 是一种非拟肽法尼基转移酶抑制剂，法尼基转移酶抑制剂（FTIs）是一类正在试验中的分子靶向抗肿瘤药物，以法尼基转移酶蛋白为靶点，具有阻止Ras蛋白正常运行的下游作用，而Ras蛋白通常在癌症中异常活跃。Ras蛋白的翻译后修饰包括四个步骤：异戊二烯基化、蛋白水解、甲基化和棕榈酰化。异戊二烯化过程涉及法尼基转移酶（FTase），将法尼基从法尼基焦磷酸酯（FPP）转移至RAS前蛋白。 此外，相关酶香叶基香叶基转移酶I（GGTase I）可将香叶基香叶基转移至K和N-RAS。Ras蛋白需法尼基化修饰才能结合于细胞膜并发挥其传导信号的作用（Reuter et al., 2000）。 231011 pj D0127 更新作用机制内容 LXL
Trametinib 曲美替尼 Mekinist 迈吉宁 诺华制药 2013/5/29 FDA/NMPA 1.MEKINISTis a kinase inhibitor indicated as a single agent for the treatment of BRAF-inhibitor treatment-nave patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.2.MEKINIST is indicated, in combination with dabrafenib, for:(1)the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.(2).the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection.(3)the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.(4).the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.(5).the treatment of adult and pediatric patients 6 years of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial MEKINIST是一种激酶抑制剂，其适应症为：1.单药用于治疗携带BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。2.联合达拉菲尼用于：(1)携带BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。(2)携带BRAF V600E或V600K突变且完全切除后累及淋巴结的黑色素瘤患者的辅助治疗。(3)携带BRAF V600E突变的转移性非小细胞肺癌(NSCLC)。(4)没有令人满意的局部区域治疗选择的BRAF V600E突变的局部晚期或转移性间变性甲状腺癌(ATC)。(5)携带BRAF V600E突变的不可切除或转移性实体瘤成人和6岁及以上的儿童患者的治疗，且这些患者在之前的治疗后进展，没有满意的替代治疗方案。（6）需要接受系统治疗并携带BRAF V600E突变的低级别胶质瘤( LGG )患者（1岁及以上）。2019年曲美替尼首次获得NMPA批准，至2022年获批适应症包括BRAF V600突变的黑色素瘤和BRAF V600突变非小细胞肺癌。 黑色素瘤、非小细胞肺癌、甲状腺癌、实体瘤，胶质瘤 Trametinib is a reversible inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2 activation and of MEK1 and MEK2 kinase activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation. BRAF V600E mutations result in constitutive activation of the BRAF pathway which includes MEK1 and MEK2. Trametinib inhibits cell growth of various BRAF V600 mutation-positive tumors in vitro and in vivo.Trametinib and dabrafenib target two different kinases in the RAS/RAF/MEK/ERK pathway. Use of trametinib and dabrafenib in combination resulted in greater growth inhibition of BRAF V600 mutation-positive tumor cell lines in vitro and prolonged inhibition of tumor growth in BRAF V600 mutation positive tumor xenografts compared with either drug alone. 曲美替尼（Trametinib）是有丝分裂原激活的细胞外信号调节激酶1（MEK1）和MEK2激活以及MEK1和MEK2激酶活性的可逆抑制剂。MEK蛋白是细胞外信号相关激酶（ERK）途径的上游调控因子，可促进细胞增殖。BRAF V600E突变导致包括MEK1和MEK2在内的BRAF途径的组成性激活。曲美替尼（Trametinib）在体外和体内抑制各种BRAF V600突变阳性肿瘤细胞的生长。曲美替尼（Trametinib）和达拉非尼（Dabrafenib）靶向RAS/RAF/MEK/ERK通路中的两种不同激酶。与单独使用这两种药物相比，曲美替尼（Trametinib）和达拉非尼（Dabrafenib）联合用药可加强对BRAF V600突变阳性<E998B3><E680A7>
Trastuzumab 曲妥珠单抗 Herceptin 赫赛汀 罗氏制药 1998/9/25 FDA/NMPA Herceptin is a HER2/neu receptor antagonist indicated for: 1.The treatment of HER2-overexpressing breast cancer. 2.The treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. Herceptin是一种HER2/neu受体拮抗剂，其适应症为：1.HER2过表达的乳腺癌。2.HER2过表达的转移性胃或胃食管交界处腺癌。2020年NMPA批准曲妥珠单抗适用于乳腺癌患者和胃腺癌或胃食管交界腺癌患者的治疗。 乳腺癌、胃癌、胃食管交界处腺癌 The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, which is structurally related to the epidermal growth factor receptor. Herceptin has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2.Herceptin is a mediator of antibody-dependent cellular cytotoxicity (ADCC). In vitro, Herceptin-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2. HER2（或c-erbB2）原癌基因编码一个185 kDa的跨膜受体蛋白，该蛋白在结构上与表皮生长因子受体有关。曲妥珠单抗/赫赛汀（Trastuzumab/Herceptin）在体外及动物实验中均显示出可抑制HER2过表达肿瘤细胞的增殖。曲妥珠单抗/赫赛汀（Trastuzumab/Herceptin）是抗体依赖性细胞毒性（ADCC）的介体。在体外研究中，与未过表达HER2的癌细胞相比，曲妥珠单抗/赫赛汀（Trastuzumab/Herceptin）介导的ADCC优先作用于过表达HER2的癌细胞。 FDA-approval:11/2018;NMPA-approval:2020 2023/6/20 sxz D0130
Tucatinib 妥卡替尼 Tukysa Seagen 2020/4/17 FDA TUKYSA is a kinase inhibitor indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. TUKYSA是一种激酶抑制剂，其适应证为：1.联合曲妥珠单抗和卡培他滨治疗既往转移治疗中接受过一种或多种抗HER2治疗的晚期不可切除性或转移性HER2阳性乳腺癌成人患者，包括发生脑转移的患者。2.联合曲妥珠单抗治疗患者之前在氟嘧啶、奥沙利铂和伊立替康化疗治疗后进展的RAS野生型，HER2阳性不可切除或转移性结直肠癌患者，。 乳腺癌 Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti- tumor activity in HER2 expressing tumor cells. In vivo, tucatinib inhibited the growth of HER2 expressing tumors. The combination of tucatinib and trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either drug alone. Tucatinib是HER2的酪氨酸激酶抑制剂。 在体外试验中，Tucatinib能够抑制HER2和HER3磷酸化，从而抑制下游MAPK和AKT信号通路和细胞增殖，并且在表达HER2的肿瘤细胞中显示出抗肿瘤活性。在体内研究中，Tucatinib可以抑制表达HER2肿瘤的生长。与单独使用这两种药物相比，Tucatinib和曲妥珠单抗（Trastuzumab)联合在体外试验和体内研究中均表现出增强的抗肿瘤活性。 01/2023 2023/4/6 sxz D0131 修改适应证 pj
Vandetanib 凡德他尼 Caprelsa 健赞 2011/4/6 FDA CAPRELSA is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. Use CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease only after careful consideration of the treatment related risks of CAPRELSA. CAPRELSA是一种激酶抑制剂，适用于治疗不能切除，局部晚期或转移的有症状或进展的髓样甲状腺癌。 甲状腺癌 ZD-6474 is a potent and selective inhibitor of VEGFR (vascular endothelial growth factor receptor), EGFR (epidermal growth factor receptor) and RET (REarranged during Transfection) tyrosine kinases.VEGFR- and EGFR-dependent signalling are both clinically validated pathways in cancer, including non-small-cell lung cancer (NSCLC). RET activity is important in some types of thyroid cancer, and early data with vandetanib in medullary thyroid cancer has led to orphan-drug designation by the regulatory authorities in the USA and EU. 凡德他尼(Vandetanib)是一种有效的血管内皮生长因子受体（VEGFR）、表皮生长因子受体（EGFR）和转染期间重排（RET）酪氨酸激酶的选择性抑制剂。VEGFR和EGFR依赖性信号途径都已在癌症，包括非小细胞肺癌（NSCLC）中经过临床验证。RET活性在某些类型的甲状腺癌中非常重要，而凡德他尼(Vandetanib)在甲状腺髓样癌中的早期数据已使美国和欧盟监管机构指定其作为甲状腺癌的孤儿药。 06/2020 2021/11/26 D0132
Vemurafenib 维莫非尼 Zelboraf 佐博伏 罗氏制药 2011/8/17 FDA/NMPA 1.ZELBORAF is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.2.ZELBORAF is indicated for the treatment of patients with Erdheim-Chester Disease with BRAF V600 mutation. ZELBORAF是一种激酶抑制剂，其适应症为：1.携带BRAF V600E突变的不可切除性或转移性黑色素瘤。2.携带BRAF V600突变的Erdheim-Chester病。2017年NMPA批准维莫非尼适用于性黑色素瘤患者的治疗。 黑色素瘤、Erdheim-Chester病 Vemurafenib is a low molecular weight, orally available inhibitor of some mutated forms of BRAF serine- threonine kinase, including BRAF V600E. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5, and FGR at similar concentrations. Some mutations in the BRAF gene including V600E result in constitutively activated BRAF proteins, which can cause cell proliferation in the absence of growth factors that would normally be required for proliferation. Vemurafenib has anti-tumor effects in cellular and animal models of melanomas with mutated BRAF V600E. 维罗非尼（Vemurafenib）是一种低分子量、口服可吸收的BRAF丝氨酸-苏氨酸激酶突变体（包括BRAF V600E）抑制剂。维罗非尼（Vemurafenib）还可以在体外以相似的浓度抑制其他激酶活性，如CRAF、ARAF、野生型BRAF、SRMS、ACK1、MAP4K5和FGR。包括V600E在内的BRAF基因突变会导致BRAF蛋白被组成性激活，从而在缺乏生长因子（通常在细胞增殖中必需）的情况下引起细胞增殖。维罗非尼（Vemurafenib）在BRAF V600E突变黑素瘤的细胞和动物模型中具有抗肿瘤作用。 FDA-approval:05/2020;NMPA-approval:2017 2023/6/20 sxz D0133
Venetoclax 维奈克拉 Venclexta 唯可来 AbbVie Ireland NL B.V. 2016/4/11 FDA/NMPA VENCLEXTA is a BCL-2 inhibitor indicated:1. For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). 2.In combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy VENCLEXTA是一种BCL-2抑制剂，其适应症为：1.慢性淋巴细胞白血病(CLL)或小淋巴细胞淋巴瘤(SLL)成人患者。2.联合阿扎胞苷、地西他滨或小剂量阿糖胞苷用于治疗年龄≥75岁或存在不适合使用强化化疗合并症的初诊急性髓系白血病(AML)。 慢性淋巴细胞白血病、小淋巴细胞淋巴瘤、急性髓系白血病 Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an anti- apoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL and AML cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outermembrane permeabilization and the activation of caspases. In nonclinical studies, venetoclax has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2. 维奈克拉(Venetoclax)是BCL-2(一种抗凋亡蛋白)的选择性和口服生物小分子抑制剂。目前已在CLL和AML细胞中证实了BCL-2的过表达，其介导肿瘤细胞的存活并与化疗抵抗有关。维奈克拉(Venetoclax)通过直接与BCL-2蛋白结合，置换促凋亡蛋白（如BIM），触发线粒体外膜通透性和半胱氨酸蛋白酶的激活来帮助恢复细胞凋亡。在非临床研究中，维奈克拉(Venetoclax)已显示出对过表达BCL-2的肿瘤细胞具有细胞毒活性。 10/2021 2021/11/26 D0134
Vismodegib 维莫德吉 Erivedge 基因泰克 2012/1/30 FDA ERIVEDGE (vismodegib) is a hedgehog pathway inhibitor indicated for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery and who are not candidates for radiation. ERIVEDGE（vismodegib）是一种hedgehog通路抑制剂，适用于手术后复发、没有手术指征或没有放疗指征的转移性或局部晚期基底细胞癌成人患者。 基底细胞癌 Vismodegib is an inhibitor of the Hedgehog pathway. Vismodegib binds to and inhibits Smoothened, a transmembrane protein involved in Hedgehog signal transduction. 维莫德吉（Vismodegib）是一种Hedgehog信号通路抑制剂。维莫德吉（Vismodegib）可结合并抑制跨膜蛋白Smoothened的活性，该蛋白参与Hedgehog信号转导。 07/2020 2021/11/26 D0135
Vistusertib Vistusertib is under investigation for the treatment of Advanced Gastric Adenocarcinoma. Vistusertib (AZD2014) 是一种ATP竞争性的 mTOR 抑制剂，IC50 为 2.81 nM。AZD2014 抑制 mTORC1 和 mTORC2 复合物。 Vistusertib正处于晚期胃腺癌治疗的研究中。 231008 pj D0136 新增作用机制内容 LXL
Vorinostat 伏立诺他 Zolinza 默克 2006/10/6 FDA ZOLINZA is a histone deacetylase (HDAC) inhibitor indicated for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. ZOLINZA是一种组蛋白去乙酰化酶(HDAC)抑制剂，用于治疗在两种全身治疗期间或之后出现进展，持续或复发疾病的的皮肤T细胞淋巴瘤(CTCL)患者的皮肤表现。 皮肤T细胞淋巴瘤 Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II) at nanomolar concentrations (IC50< 86 nM). These enzymes catalyze the removal of acetyl groups from the lysine residues of histones proteins. In some cancer cells, there is an overexpression of HDACs, or an aberrant recruitment of HDACs to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones. By inhibiting histone deacetylase, vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of vorinostat has not been fully characterized. 伏立诺他(Vorinostat)可在纳摩尔级浓度下抑制组蛋白脱乙酰基酶HDAC1、HDAC2和HDAC3（I类）和HDAC6（II类）的酶活性（IC50 < 86 nM）。这些酶催化去除组蛋白赖氨酸残基上的乙酰基基团。在某些肿瘤细胞中，HDACs过表达，或异常募集到致癌的转录因子上，导致核小体核心组蛋白乙酰化不足。伏立诺他(Vorinostat)通过抑制组蛋白脱乙酰基酶来导致乙酰化组蛋白的累积，并诱导某些转化细胞的细胞周期停滞和/或凋亡。伏立诺他(Vorinostat)抗肿瘤作用的机制尚未完全阐明。 12/2018 2021/11/26 pj/sjz D0137
Mobocertinib 莫博赛替尼 Exkivity 安卫力 Takeda Pharms USA 2023/1/26 0:00 FDA/NMPA EXKIVITY is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, , whose disease has progressed on or after platinum-based chemotherapy. EXKIVITY是一种激酶抑制剂，适用于具有表皮生长因子受体(EGFR)外显子20插入突变、既往接受铂类化疗期间或之后疾病进展的局部晚期或转移性非小细胞肺癌(NSCLC)成人患者。2023年，中国药监局发布公告，通过优先审评审批程序附条件批准武田制药公司申报的1类创新药琥珀酸莫博赛替尼胶囊（商品名：安卫力/EXKIVITY）上市。主要用于治疗含铂化疗期间或之后进展且携带表皮生长因子受体（EGFR）20号外显子插入突变的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。 非小细胞肺癌 Mobocertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR) that irreversibly binds to and inhibits EGFR exon 20 insertion mutations at lower concentrations than wild type (WT) EGFR. Two pharmacologically-active metabolites (AP32960 and AP32914) with similar inhibitory profiles to mobocertinib have been identified in the plasma after oral administration of mobocertinib. In vitro, mobocertinib also inhibited the activity of other EGFR family members (HER2 and HER4) and one additional kinase (BLK) at clinically relevant concentrations (IC50 values <2 nM). In cultured cell models, mobocertinib inhibited the proliferation of cells driven by different EGFR exon 20 insertion mutation variants at 1.5- to 10-fold lower concentrations than WT-EGFR signaling inhibition.In animal tumor implantation models, mobocertinib exhibited anti-tumor activity against xenografts with the EGFR exon 20 insertions NPH or ASV. Mobocertinib是一种表皮生长因子受体（EGFR）激酶抑制剂，其不可逆结合并抑制EGFR外显子20插入突变的浓度低于野生型（WT）EGFR。口服Mobocertinib后，在血浆中发现两种具有类似Mobocertinib抑制特性的药理活性代谢物（AP32960和AP32914）。在体外试验中，Mobocertinib在临床相关浓度（IC50值<2 nM）下也可抑制其他EGFR家族成员（HER2和HER4）和一种额外激酶（BLK）的活性。在培养的细胞模型中，Mobocertinib可抑制由不同EGFR外显子20插入突变驱动的细胞增殖，其浓度比抑制WT-EGFR的浓度低1.5-10倍。在动物肿瘤植入模型中，Mobocertinib对EGFR外显子20插入NPH或ASV的异种移植物具有抗肿瘤活性。 09/2021 2023/5/26 0:00 SXZ D0139 名称修改 LXL
Margetuximab-cmkb 马吉妥昔单抗 Margenza 麦甘乐 Macrogenics Inc 2020/12/16 0:00 FDA/NMPA MARGENZA is a HER2/neu receptor antagonist indicated, in combination with chemotherapy, for the treatment of adult patients with metastatic HER2- positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Margetuximab-cmkb是一种HER2/neu受体拮抗剂，适用于联合化疗治疗既往接受两种或两种以上抗HER2方案(其中至少一种用于转移性疾病)的转移性HER2阳性乳腺癌成人患者。2023年8月29日，NMPA批准马吉妥昔单抗（Margetuximab-cmkb）在国内上市，用于转移性HER2阳性乳腺癌患者三线及以上治疗。 乳腺癌 Margetuximab-cmkb binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2). Upon binding to HER2-expressing tumor cells, margetuximab-cmkb inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain and mediates antibody-dependent cellular cytotoxicity (ADCC).In vitro, the modified Fc region of margetuximab-cmkb increases binding to activating Fc receptor FCGR3A (CD16A) and decreases binding to inhibitory Fc receptor FCGR2B (CD32B). These changes lead to greater in vitro ADCC and NK cell activation. Margetuximab-cmkb与人表皮生长因子受体2蛋白（HER2）的胞外结构域结合。与表达HER2的肿瘤细胞结合后，margetuximab-cmkb可抑制肿瘤细胞增殖，减少HER2胞外结构域的脱落，并介导抗体依赖性细胞毒性（ADCC）。在体外试验中，经修饰的margetuximab-cmkb的Fc区增加了与激活的Fc受体FCGR3A（CD16A）的结合亲和力，并减少了与抑制性Fc受体FCGR2B（CD32B）的结合。这些改变导致更强的体外ADCC和NK细胞活化作用。 12/2020 231016 pj D0140 补充NMPA批准信息
Darolutamide 达罗他胺 Nubeqa 诺倍戈 拜耳医药 2019/7/30 FDA/NMPA NUBEQA is an androgen receptor inhibitor indicated for the treatment of adult patients with: non-metastatic castration-resistant prostate cancer (nmCRPC). metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel NUBEQA是一种雄激素受体抑制剂，适用于非转移性去势抵抗性前列腺癌患者。联合多西他赛适应于转移性激素敏感性前列腺癌。2021年NMPA批准达罗他胺适用于性前列腺癌患者的治疗 前列腺癌 Darolutamide is an androgen receptor (AR) inhibitor. Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. A major metabolite, keto-darolutamide, exhibited similar in vitro activity to darolutamide. In addition, darolutamide functioned as a progesterone receptor (PR) antagonist in vitro (approximately 1% activity compared to AR). Darolutamide decreased prostate cancer cell proliferation in vitro and tumor volume in mouse xenograft models of prostate cancer. darolutamide是雄激素受体( AR )抑制剂。Darolutamide竞争性地抑制雄激素与雄激素受体(AR)配体结合位点的结合，抑制转录因子AR的核易位，并抑制靶基因的转录。主要代谢产物酮基-达罗他胺(keto-darolutamide)也表现出相似的体外活性。此外，达罗他胺（darolutamide）也是孕激素受体（PR）拮抗剂，体外活性约为AR的1%。在前列腺癌的小鼠异种移植模型中，达罗他胺（darolutamide）可以降低体外前列腺癌细胞增殖和肿瘤体积。 FDA-approval:08/2022 2023/6/20 sxz D0143 适应症更新
Adagrasib 阿达格拉西布 KRAZATI MIRATI THERAPS 1905/7/14 FDA KRAZATI is an inhibitor of the RAS GTPase family indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA approved test, who have received at least one prior systemic therapy KRAZATI是RAS GTPase家族的抑制剂，用于治疗FDA批准的KRAS G12C突变的局部晚期或转移性非小细胞肺癌的成人患者（(FDA-approval:12/2022) 非小细胞肺癌 Adagrasib is an irreversible inhibitor of KRAS G12C that covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state that prevents downstream signaling without affecting wild-type KRAS protein. Adagrasib inhibits tumor cell growth and viability in cells harboring KRAS G12C mutations and results in tumor regression in KRAS G12C-mutated tumor xenograft models with minimal off-target activity. Adagrasib是KRAS G12C的一种不可逆抑制剂，它与KRAS G12C中的突变半胱氨酸共价结合，并将突变KRAS蛋白锁定在其非活性状态，从而阻止下游信号传导，而不影响野生型KRAS蛋白。Adagrasib抑制KRAS G12C突变细胞的肿瘤细胞生长和活力，并在KRAS G12C突变的肿瘤异种移植模型中以最小的脱靶活性导致肿瘤消退。 2023/1/15 sxz D0144
Ipilimumab 伊匹木单抗 Yervoy 逸沃 百时美施贵宝 2011/3/25 FDA/NMPA YERVOY is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody indicated for: 1.Melanoma:(1):Treatment of unresectable or metastatic melanoma in adults and pediatric patients 12 years and older.(2):Treatment of adult patients with unresectable or metastatic melanoma, in combination with nivolumab. (2).Adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy. 2.Renal Cell Carcinoma (RCC):Treatment of patients with intermediate or poor risk advanced renal cell carcinoma, as first-line treatment in combination with nivolumab. 3.Colorectal Cancer:Treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, in combination with nivolumab.4.Hepatocellular Carcinoma:Treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib, in combination with nivolumab. 5.Non-Small Cell Lung Cancer (NSCLC):(1).Treatment of adult patients with metastatic non-small cell lung cancer expressing PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with nivolumab. (2).Treatment of adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations as first-line treatment, in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy. 6.Malignant Pleural Mesothelioma:Treatment of adult patients with unresectable malignant pleural mesothelioma, as first-line treatment in combination with nivolumab.7.Esophageal Cancer: Treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, as first line treatment in combination with nivolumab. YERVOY是一种抗CTLA-4单克隆抗体，其适应症为：1.黑色素瘤：(1)转移性或不可切除的成人与儿童（ ≥12岁）黑色素瘤患者。(2)联合纳武利尤单抗用于治疗转移性或不可切除的黑色素瘤成人患者。(3)皮肤黑色素瘤患者的辅助治疗，该患者病理累及淋巴结超过1mm且已进行完全切除，包括全淋巴结切除术。2.肾细胞癌(RCC)：与纳武利尤单抗联合用于中危或低危晚期肾细胞癌患者的一线治疗。 3.结直肠癌：与纳武利尤单抗联合用于治疗接受氟嘧啶、奥沙利铂、伊立替康治疗后进展的微卫星高度不稳定(MSI-H)或错配修复缺陷(dMMR)的转移性结直肠癌成人和儿童（ ≥12岁）患者。4.肝细胞癌：与纳武利尤单抗联合用于治疗既往接受索拉非尼治疗的肝细胞癌患者。5.非小细胞肺癌(NSCLC)：(1)与纳武利尤单抗联合用于表达PD-L1(≥1%)、无EGFR或ALK基因组肿瘤畸变的转移性NSCLC成人患者的一线治疗。(2)与纳武利尤单抗以及两周期的含铂双药化疗联合，用于无EGFR或ALK基因组肿瘤畸变的转移性或复发性NSCLC成人患者的一线治疗。6.恶性胸膜间皮瘤：与纳武利尤单抗联合用于不可切除的恶性胸膜间皮瘤成人患者的一线治疗。7.食管癌:联合纳武利尤单抗作为不可切除的晚期或转移性食管癌成人患者的一线治疗方案。2021年NMPA批准用于不可切除的恶性胸膜间皮瘤。 黑色素瘤、肾细胞癌、结直肠癌、肝细胞癌、非小细胞肺癌、恶性胸膜间皮瘤、食管癌 CTLA-4 is a negative regulator of T-cell activity. Ipilimumab is a monoclonal antibody that binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduc
Zanubrutinib 泽布替尼 Brukinsa 百悦泽 百济神州 2019/11/14 FDA/NMPA BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with: 1.Mantle cell lymphoma (MCL) who have received at least one prior therapy. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 2.Waldenstrm’s macroglobulinemia (WM). 3.Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen. BRUKINSA是一种激酶抑制剂，其适应症为：1.适用于既往曾接受过至少一次治疗的套淋巴瘤(MCL)成人患者。2.华氏巨球蛋白血症(WM)。3.既往接受过至少一次抗CD20方案的复发或难治性边缘区淋巴瘤(MZL)。4.慢性淋巴细胞白血病( CLL )或小淋巴细胞淋巴瘤( SLL )。 淋巴瘤、华氏巨球蛋白血症 Zanubrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK). Zanubrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion. In nonclinical studies, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth. 泽布替尼是Bruton酪氨酸激酶( BTK )的小分子抑制剂。泽布替尼与BTK活性位点中的半胱氨酸残基形成共价键，导致BTK活性的抑制。BTK是B细胞抗原受体( BCR )和细胞因子受体途径的信号传导分子。在B细胞中，BTK信号传导激活了B细胞增殖、运输、趋化和粘附所必需的途径。在非临床研究中，泽布替尼抑制恶性B细胞增殖并减少肿瘤生长。 01/2023 2023/4/6 sxz D0153 修改适应证 pj
Orelabrutinib 奥布替尼 宜诺凯 合全药业 2020/12/25 NMPA 奥布替尼是一种选择性Bruton酪氨酸激酶(BTK)抑制剂，其适应症为：1.既往接受过至少一种治疗的成人套细胞淋巴瘤(MCL)患者。2.既往接受过至少一种治疗的成人慢性淋巴细胞白血病(CLL)/小淋巴细胞淋巴瘤(SLL)患者。3.既往至少接受过一种治疗的成人边缘区淋巴瘤（MZL）患者 淋巴瘤、白血病 奥布替尼为选择性 Bruton 酪氨酸激酶（BTK）抑制剂，对 BTK 抑制作用的IC50 为 1.6 nM。BTK 为 B 细胞抗原受体（BCR）和细胞因子受体通路的信号分子，通过 B 细胞表面受体活化的信号通路为 B 细胞迁徙、趋化和黏附的必需途径。本品可抑制 BTK 相关信号通路的激活，抑制 B 细胞的过度活化和增殖。 12/2020 2023/4/6 sxz D0154 适应证修改 pj
Acalabrutinib 阿可替尼 Calquence 康可期 AstraZeneca Pty Ltd 2017/10/31 0:00 FDA/NMPA CALQUENCE is a kinase inhibitor indicated for the treatment of adult patients with: 1.Mantle cell lymphoma (MCL) who have received at least one prior therapy. 2.Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). CALQUENCE是一种激酶抑制剂，其适应症为：1 .已接受过至少一次治疗的套细胞淋巴瘤(MCL)成年患者。2. 慢性淋巴细胞白血病(CLL)或小淋巴细胞淋巴瘤(SLL)成年患者。2023年，NMPA批准阿可替尼胶囊附条件批准上市，用于既往至少接受过一种治疗的成人套细胞淋巴瘤（MCL）患者。 淋巴瘤、白血病 Acalabrutinib is a small-molecule inhibitor of BTK. Acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B cell antigen receptor (BCR) and cytokine receptor pathways. In B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. In nonclinical studies, acalabrutinib inhibited BTK-mediated activation of downstream signaling proteins CD86 and CD69 and inhibited malignant B-cell proliferation and tumor growth in mouse xenograft models. Acalabrutinib是BTK的小分子抑制剂。Acalabrutinib及其活性代谢物ACP - 5862与BTK活性位点的一个半胱氨酸残基形成共价键，从而抑制BT的K酶活性。BTK是B细胞抗原受体( BCR )和细胞因子受体通路的信号分子。BTK信号传导会激活B细胞增殖、运输、趋化和粘附所必需的途径。在非临床研究中，抑制acalabrutinib下游信号蛋白CD86和CD69，BTK的介导的激活，并在小鼠异种移植模型中抑制恶性B细胞增殖和肿瘤生长。 11/2019 2023/5/26 0:00 SXZ D0156 批准单位与名称修改 LXL
Selinexor 塞利尼索 Xpovio Karyopharm Theraps 1905/7/11 FDA/NMPA XPOVIO is a nuclear export inhibitor indicated: 1. In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. 2. In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody. 3. For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 塞利尼索是一种核输出抑制剂，其适应症包括：1.联合Bortezomib和Dexamethasone用于既往至少接受过一次治疗的多发性骨髓成人瘤患者。2.联合Dexamethasone用于治疗既往接受过至少4种疗法且对至少2种蛋白酶体抑制剂、至少2种免疫抑制剂、1种CD38单克隆抗体耐药的难治复发性多发性成人骨髓瘤患者。3.适用于至少经过2线治疗的复发或难治性成人弥漫大B细胞淋巴瘤(DLBCL)（若无特别说明，则包括滤泡性淋巴瘤引起的DLBCL）。 多发性骨髓瘤、弥漫性大B细胞淋巴瘤 In nonclinical studies, selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). XPO1 inhibition by selinexor leads to accumulation of TSPs in the nucleus and reductions in several oncoproteins, such as c‐myc and cyclin D1,cell cycle arrest, and apoptosis of cancer cells. Selinexor demonstrated pro‐apoptotic activity in vitro in multiple myeloma cells and showed anti‐tumor activity in murine xenograft models of multiple myeloma and diffuse large B cell lymphoma. The combination of selinexor and dexamethasone or bortezomib demonstrated synergistic cytotoxic effects in multiple myeloma in vitro and increased anti‐tumor activity in murine xenograft multiple myeloma models in vivo, including those resistant to proteasome inhibitors. 在非临床研究中，Selinexor通过抑制核输出蛋白-1(XPO1)可逆地抑制肿瘤抑制蛋白(TSPs)、生长调节蛋白和致癌蛋白mRNA的核输出。进而导致了细胞核中TSPs的积累、c‐myc和cyclinD1等几种癌蛋白的减少，细胞周期阻滞和癌细胞的凋亡。Selinexor在体外多发性骨髓瘤细胞中显示促凋亡活性，在多发性骨髓瘤和弥漫性大B细胞淋巴瘤异种移植小鼠模型中显示抗肿瘤活性。Selinexor联合地塞米松或硼替佐米在体外多发性骨髓瘤中具有协同细胞毒作用，且在体内异种移植多发性骨髓瘤小鼠模型中增强抗肿瘤活性（包括对蛋白酶体抑制剂耐药的小鼠）。 2020/12/1 2022/1/24 sxz D0159
Inotuzumab 奥加伊妥珠单抗 Besponsa 贝博萨 Wyeth Pharms Inc 2017 FDA/NMPA BESPONSA is a CD22-directed antibody-drug conjugate (ADC) indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Inotuzumab是一种CD22靶向的抗体-药物偶联物(ADC)，用于治疗复发或难治性前体B细胞急性淋巴细胞性白血病(ALL)。适用于成人复发或难治性前B细胞急性淋巴细胞性白血病。 白血病 Inotuzumab ozogamicin is a CD22-directed antibody-drug conjugate (ADC). Inotuzumab recognizes human CD22. The small molecule, N-acetyl-gamma-calicheamicin, is a cytotoxic agent that is covalently attached to the antibody via a linker. Nonclinical data suggest that the anticancer activity of inotuzumab ozogamicin is due to the binding of the ADC to CD22-expressing tumor cells, followed by internalization of the ADC-CD22 complex, and the intracellular release of N-acetyl-gamma-calicheamicin dimethylhydrazide via hydrolytic cleavage of the linker. Activation of N-acetyl-gamma-calicheamicin 19 Reference ID: 4140675 dimethylhydrazide induces double-strand DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death. Inotuzumab是一种靶向CD22的抗体-药物偶联物(ADC)，可以识别人CD22。小分子N-乙酰-γ卡奇霉素，是通过接头与抗体共价连接的细胞毒性剂。非临床数据表明，Inotuzumab的抗肿瘤活性是由于ADC与表达CD22的肿瘤细胞相结合，随后ADC-CD22被细胞内化，并且细胞内释放通过连接子水解裂解的N-乙酰-γ-卡里奇霉素二甲基酰肼。N-乙酰-γ-卡里奇霉素二甲基酰肼的活化诱导双链DNA断裂，随后诱导细胞周期停滞和凋亡细胞死亡。 08/2017 2022/1/24 0:00 sxz D0160 修改日期；sxz LXL
Dovitinib 多韦替尼 Dovitinib is an orally active small molecule that exhibits potent inhibitory activity against multiple RTKs involved in tumor growth and angiogenesis. Preclinical data show that dovitinib works to inhibit multiple kinases associated with different cancers.Unlike many kinase inhibitors that only target vascular endothelial growth factor (VEGF), Dovitinib inhibits receptors in the fibroblast growth factor (FGF ) pathway, as well as VEGF and platelet-derived growth factor (PDGF). Dovitinib是一种口服活性小分子，可抑制参与肿瘤生长和血管生成的多种RTKs（蛋白酪氨酸激酶）。临床前数据显示，Dovitinib可抑制与不同癌症相关的多种激酶，包括急性髓系白血病(AML)和多发性骨髓瘤。与许多只针对血管内皮生长因子(VEGF)的激酶抑制剂不同，Dovitinib抑制成纤维细胞生长因子(FGF)通路中的受体，以及VEGF和血小板衍生生长因子(PDGF)，Dovitinib在体内诱导细胞抑制和细胞毒性应答，导致表达FGFR3的肿瘤细胞消退。 在一项临床前研究中Dovitinib (TKI258)抑制了培养物中转化（FGFR3 S249C）细胞的生长。 231011 pj D0165 更新药物中文名称 LXL
GI-4000 GI-4000, a vaccine containing a heat-killed recombinant Saccharomyces cerevisiae yeast transfected with mutated forms of Ras, an oncogene frequently found in solid tumors, with potential immunostimulant and antitumor activity. Upon administration, GI-4000 vaccine elicits an immune response by stimulating a specific cytotoxic T-cell response against the mutated forms of Ras. This may lead to a destruction of cancer cells expressing a Ras mutation. GI-4000是一种含有高温灭火的携带有Ras突变的重组酿酒的疫苗，Ras是一种在实体瘤中常见的癌基因，具有潜在的免疫刺激和抗肿瘤活性。给药时，GI-4000会刺激针对Ras突变的细胞毒性T细胞免疫反应，这可能会使Ras突变的癌细胞被消除。 I期临床试验，RAS突变的胰腺癌患者使用GI-4000治疗耐受性良好，并诱导了一定的RAS定向免疫应答。 231011 pj D0166 修订作用机制-英文内容 LXL
Depatuxizumab mafodotin Depatuxizumab is a chimeric monoclonal antibody for EGFR which is linked to monomethyl aurastatin F via a maleimidocaproyl linker (mafodotin) 1. Once delivered to the cancer cell, the mafodotin component is able to bind to tubulin and inhibit the exchange of GDP for GTP necessary for the polymerization of tubulin subunits to form microtubules. The inhibition of microtubule polymerization disrupts mitosis and interferes with vesicle trafficking in the cancer cell. Depatuxizumab是一种靶向EGFR的嵌合单克隆抗体，它通过mafodotin连接到MonomethylaurastatinF(MMAF，一种合成抗肿瘤药，是微管聚合的抑制剂)。一旦输入癌细胞，Mafodotin与微管蛋白结合，并抑制GDP对微管蛋白亚基聚合形成微管所必需的GTP的交换。微管聚合的抑制扰乱了癌细胞的有丝分裂，干扰了癌细胞内囊泡的运输。 在一项I/II期试验中，对携带EGFR扩增、过度表达或突变的晚期实体瘤患者，Depatuxizumab-Mafoodtin（ABT-414）治疗的部分缓解率为1.8%（1/56），稳定疾病的发生率为23%（13/56）。 2022/1/24 sxz D0169
Ribociclib 瑞波西利 Kisqali 凯丽隆 Novartis Pharma Schweiz AG 2017/3/13 0:00 FDA/NMPA KISQALI is a kinase inhibitor indicated for the treatment of adult patients with hormone receptor (HR)- positive, human epidermal growth factor receptor 2 (HER2)- negative advanced or metastatic cancer in combination with: 1.an aromatase inhibitor as initial endocrine-based therapy; or fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy in postmenopausal women or in men. KISQALI是一种激酶抑制剂，其适应症为：1.联合芳香化酶抑制剂用于激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性的成人女性晚期或转移性乳腺癌的初始内分泌治疗。2.联合氟维司群用于HR阳性、HER2阴性的绝经后女性或男性晚期或转移性乳腺癌的初始内分泌治疗或内分泌治疗后疾病进展的后续治疗。2023年，琥珀酸瑞波西利片获得国家药监局批准，与芳香化酶抑制剂联合用药，作为激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性局部晚期或转移性乳腺癌绝经前或围绝经期女性患者的初始内分泌治疗，使用内分泌疗法治疗时应联用黄体生成素释放激素(LHRH)激动剂。 乳腺癌 Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and play a crucial role in signaling pathways which lead to cell cycle progression and cellular proliferation. The cyclin D- CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb).In vitro, ribociclib decreased pRb phosphorylation leading to arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer cell lines. In vivo, treatment with single agent ribociclib in a rat xenograft model with human tumor cells led to decreased tumor volumes, which correlated with inhibition of pRb phosphorylation. In studies using patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen (e.g., letrozole) resulted in increased tumor growth inhibition compared to each drug alone. Additionally, the combination of ribociclib and fulvestrant resulted in tumor growth inhibition in an estrogen receptor positive breast cancer xenograft model. Ribociclib是细胞周期蛋白依赖性激酶（CDK）4和6抑制剂。这些激酶与细胞周期蛋白D结合后被激活，并在细胞周期进程和细胞增殖相关信号途径中发挥关键作用。细胞周期蛋白D-CDK4/6复合物通过视网膜母细胞瘤蛋白（pRb）的磷酸化来调节细胞周期进程。体外试验中，Ribociclib可以减少pRb磷酸化，导致细胞周期停滞在G1期，并减少乳腺癌细胞系中的增殖。在人源肿瘤细胞大鼠异种移植瘤模型中，Ribociclib单药可导致肿瘤体积缩小，这与pRb磷酸化的抑制有关。在患者源性雌激素受体阳性乳腺癌异种移植模型的研究中，与单独两个药物相比，Ribociclib和抗雌激素（如来曲唑[Letrozole]）联合可增加肿瘤生长抑制作用。此外，在雌激素受体阳性乳腺癌异种移植模型中Ribociclib和氟维司群（Fulvestrant）联合可抑制肿瘤生长。 12/2021 2023/5/26 0:00 sxz D0175 名称修改 LXL
Belzutifan Welireg Merck Sharp Dohme 2021 FDA Welireg is a hypoxia-inducible factor inhibitor indicated for treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. Welireg是一种缺氧诱导因子抑制剂，适应症包括：1. 用于需要治疗相关肾细胞癌（RCC）、中枢神经系统（CNS）血管母细胞瘤或胰腺神经内分泌肿瘤（pNET）的von Hippel-Lindau（VHL）成人患者，这些患者不需要立即手术。2. 用于治疗既往接受过PD-(L)1抑制剂和血管内皮生长因子酪氨酸激酶抑制剂（VEGF-TKI）的晚期肾细胞癌（RCC）成人患者。 肾细胞癌（RCC）、中枢神经系统（CNS）血管母细胞瘤、胰腺神经内分泌肿瘤 Belzutifan is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α). HIF-2α is a transcription factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia. Under normal oxygen levels, HIF-2α is targeted for ubiquitin-proteasomal degradation by VHL protein. Lack of functional VHL protein results in stabilization and accumulation of HIF-2α. Upon stabilization, HIF-2α translocates into the nucleus and interacts with hypoxia-inducible factor 1 beta (HIF-1β) to form a transcriptional complex that induces expression of downstream genes, including genes associated with cellular proliferation, angiogenesis, and tumor growth. Belzutifan binds to HIF-2α, and in conditions of hypoxia or impairment of VHL protein function, belzutifan blocks the HIF-2α-HIF-1β interaction, leading to reduced transcription and expression of HIF-2α target genes. In vivo, belzutifan demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma. Belzutifan是一种缺氧诱导因子2α(HIF-2α)的抑制剂。HIF-2α是一种转录因子，通过调节基因促进对缺氧的适应，在氧气感知中发挥作用。在常氧水平下，HIF-2α是VHL蛋白泛素-蛋白酶体降解的靶点。功能性VHL蛋白的缺失导致HIF-2α的稳定和积累。导致HIF-2α易位到细胞核中，并与缺氧诱导因子1β(HIF-1β)形成转录复合物，诱导下游基因的表达，包括与细胞增殖、血管生成和肿瘤生长相关的基因。Belzutifan与HIF-2α结合，在缺氧或VHL蛋白功能受损的条件下，Belzutifan阻断HIF-2α-HIF-1β相互作用，导致HIF-2α靶基因的转录和表达减少。在体内，belzutifan在小鼠肾细胞癌异种移植模型中显示出抗肿瘤活性。 FDA-Revised:12/2023 2023-12-18 00:00:00 pj D0176 更新适应症信息
PC14586 An orally bioavailable, small molecule reactivator of the p53 Y220C mutant, with potential antineoplastic activity. Upon oral administration, p53 Y220C mutant reactivator PC14586 selectively targets and binds to the crevice created by the p53 Y220C mutation, which normalizes and restores wild-type p53 protein structure and activity. This blocks tumor cell cycle progression and induces apoptosis in tumor cells expressing the p53 Y220C mutant. The p53 gene, a tumor suppressor gene, is mutated in many tumor types. The p53 protein plays a key role in the regulation of apoptosis and cellular proliferation. PC14586 是一种口服的小分子 p53 Y220C 突变重激活剂，具有潜在的抗肿瘤活性。口服 p53 Y220C 突变重激活剂 PC14586 可选择性地靶向 p53 Y220C 突变产生的缝隙并与之结合，从而使野生型 p53 蛋白结构和活性恢复正常。这将阻止肿瘤细胞周期的进展，并诱导表达 p53 Y220C 突变体的肿瘤细胞凋亡。p53 基因是一种肿瘤抑制基因，在许多肿瘤类型中都会发生突变。p53 蛋白在调节细胞凋亡和细胞增殖方面起着关键作用。 PC14586在临床前物种中耐受性良好，并具有良好的发展特征。PC14586的安全性和有效性目前正在一项I / II期临床研究中进行评估。临床研究确定局部晚期或转移性TP53 Y220C突变实体瘤的成人患者最大耐受剂量和推荐的2期剂量，结果表明，在21个符合条件的患者中5名患者观察到PR现象，3个最高剂量组中10个符合条件的患者有3个PR和7个SD。且观察到携带P53 Y220C突变的循环肿瘤DNA和周肿瘤数量均下降。（Abstract: Dumbrava et al. Abstract# 3003, ASCO 2022; Abstract: Dumble et al. Abstract# LB006, AACR 2021） 231011 pj D0181 更新作用机制内容 LXL
RLY-2608 An orally bioavailable, pan-mutant selective inhibitor of the class I phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha (phosphoinositide 3-kinase alpha; PIK3CA; PI3K p110alpha), with potential antineoplastic activity. Upon oral administration, pan-mutant selective PI3K-alpha inhibitor RLY-2608 selectively targets and allosterically binds to PIK3CA mutated forms, thereby preventing the activity of PIK3CA mutants. This prevents mutant PIK3CA-mediated activation of the PI3K/Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway. This results in both apoptosis and growth inhibition in PIK3CA-mutant expressing tumor cells. By specifically targeting PIK3CA mutants, RLY-2608 may be more efficacious and less toxic than PI3K-alpha inhibitors that also inhibit the wild-type (WT) form. Dysregulation of the PI3K/Akt/mTOR pathway is often found in solid tumors and results in the promotion of tumor cell growth, survival, and resistance to chemo- and radio-therapy. PIK3CA, one of the most frequently mutated oncogenes, encodes the p110-alpha catalytic subunit of the class I PI3K. RLY-2608 是一种口服、泛突变选择性 I 类磷脂酰肌醇-4,5-二磷酸 3-激酶（PI3K）催化亚基 α（PIK3CA；PI3K p110α）抑制剂，具有潜在的抗肿瘤活性。口服后，泛突变选择性 PI3K-α 抑制剂 RLY-2608 可选择性地靶向 PIK3CA 突变并与之异源结合，从而阻止 PIK3CA 突变的活性。这可防止突变型 PIK3CA 介导的 PI3K/Akt（蛋白激酶 B）/哺乳动物雷帕霉素靶点（mTOR）通路的激活。这将导致表达 PIK3CA 突变的肿瘤细胞出现凋亡和生长抑制。通过特异性靶向 PIK3CA 突变，RLY-2608 可能比同时抑制野生型（WT）的 PI3K-α 抑制剂更有效、毒性更低。PI3K/Akt/mTOR通路的失调经常出现在实体瘤中，并导致肿瘤细胞的生长、存活以及对化疗和放疗的耐药性。PIK3CA 是最常发生突变的致癌基因之一，它编码 I 类 PI3K 的 p110-α 催化亚基。 231011 pj D0182 更新作用机制内容 LXL
LOXO-783 An orally bioavailable, brain penetrative, selective irriversible inhibitor of the class I phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha (phosphoinositide 3-kinase alpha; PIK3CA; PI3K p110alpha) mutant H1047R, with potential antineoplastic activity. Upon oral administration, mutant-selective PI3K-alpha H1047R inhibitor LOXO-783 selectively targets and allosterically binds to the PIK3CA mutated form PI3Ka H1047R, thereby preventing the activity of the H1047R mutant. This prevents PIK3CA H1047R-mediated activation of the PI3K/Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway. This results in both apoptosis and growth inhibition in PIK3CA H1047R-mutant expressing tumor cells. By specifically targeting the PIK3CA H1047R mutation, LOXO-783 may be more efficacious and less toxic than other PI3K-alpha inhibitors that are not mutant specific. Dysregulation of the PI3K/Akt/mTOR pathway is often found in solid tumors and results in the promotion of tumor cell growth, survival, and resistance to chemo- and radio-therapy. PIK3CA, one of the most frequently mutated oncogenes, encodes the p110-alpha catalytic subunit of the class I PI3K. LOXO-783 is able to penetrate the blood-brain-barrier (BBB). LOXO-783 是一种口服、脑穿透性、选择性的 I 类磷脂酰肌醇-4,5-二磷酸 3-激酶（PI3K）催化亚基 α（PIK3CA；PI3K p110α） H1047R 突变的不可逆抑制剂，具有潜在的抗肿瘤活性。口服后，突变选择性 PI3K-α H1047R 抑制剂 LOXO-783 选择性地靶向 PIK3CA 突变形式 PI3Ka H1047R 并与之异源结合，从而阻止 H1047R 突变的活性。这就阻止了 PIK3CA H1047R 介导的 PI3K/Akt（蛋白激酶 B）/哺乳动物雷帕霉素靶点（mTOR）通路的激活。这导致了 PIK3CA H1047R 突变表达肿瘤细胞的凋亡和生长抑制。通过特异性靶向 PIK3CA H1047R 突变，LOXO-783 可能比其他不具有突变特异性的 PI3K-α 抑制剂更有效、毒性更低。PI3K/Akt/mTOR通路失调常常出现在实体瘤中，并导致肿瘤细胞的生长、存活以及对化疗和放疗的耐药性。PIK3CA 是最常发生突变的癌基因之一，编码 I 类 PI3K 的 p110-α 催化亚基。LOXO-783 能够穿透血脑屏障（BBB）。 231011 pj D0183 更新作用机制内容 LXL
BLU-222 BLU-222 is an orally available, selective investigational CDK2 inhibitor. BLU-222 是一种可口服的选择性 CDK2 抑制剂。 BLU-222是一种CDK2（细胞周期蛋白依赖性激酶）选择性抑制剂，一项临床前研究证明，BLU-222对携带CCNE1（（细胞周期蛋白E1）扩增的细胞系具有高度敏感性，且在体外研究中BLU-222对携带CCNE1扩增的异种移植（CDX）肿瘤模型具有显著的抗肿瘤活性 231008 pj D0185 新增作用机制内容 LXL
RMC-6236 An orally bioavailable inhibitor of the active, guanosine triphosphate (GTP)-bound form of both wild type and mutant variants of the RAS isoforms, including HRAS, NRAS and KRAS, with potential antineoplastic activity. Upon oral administration, RAS inhibitor RMC-6236 binds to an intracellular chaperone protein, cyclophilin A (CypA). The resulting inhibitory binary complex binds to active, GTP-bound RAS to form a tri-complex. This tri-complex inhibits RAS-dependent signaling and inhibits the proliferation of tumor cells in which RAS is overexpressed and/or mutated. RAS plays an important role in cell signaling, division and differentiation. Mutations of RAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis. RMC-6236 是一种口服生物活性的抑制剂，可抑制 RAS 同工酶（包括 HRAS、NRAS 和 KRAS）野生型和突变型变体的活性三磷酸鸟苷（GTP）结合状态，具有潜在的抗肿瘤活性。口服给药后，RAS 抑制剂 RMC-6236 会与细胞内的伴侣蛋白 cyclophilin A（CypA）结合。由此产生的抑制性二元复合物与活性的、GTP 结合的 RAS 结合形成三元复合物。这种三复合体可抑制 RAS 依赖性信号传导，并抑制 RAS 过表达和/或突变的肿瘤细胞的增殖。RAS 在细胞信号传导、分裂和分化中发挥着重要作用。RAS 基因突变可诱导组成型信号转导，导致肿瘤细胞生长、增殖、侵袭和转移。 231008 pj D0186 新增作用机制内容 LXL
Elacestrant 艾拉司群 Orserdu Stemline Therapeutics Inc 1905/7/15 FDA ORSERDU is an estrogen receptor antagonist indicated for: treatment of postmenopausal women or adult men, with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy ORSERDU是一种雌激素受体拮抗剂，FDA推荐用于携带ER阳性、HER2阴性、ESR1突变的晚期或转移性乳腺癌绝经女性或成年男性，且其之前在至少一条内分泌治疗后疾病进展。 乳腺癌 Elacestrant is an estrogen receptor antagonist that binds to estrogen receptor-alpha (ERα). In ER-positive (ER+) HER2-negative (HER2-) breast cancer cells, elacestrant inhibited 17β-estradiol mediated cell proliferation at concentrations inducing degradation of ERα protein mediated through proteasomal pathway. Elacestrant demonstrated in vitro and in vivo antitumor activity including in ER+ HER2- breast cancer models resistant to fulvestrant and cyclin-dependent kinase 4/6 inhibitors and those harboring estrogen receptor 1 gene (ESR1) mutations. Elacestrant是一种与雌激素受体α（ERα）结合的雌激素受体拮抗剂,在（ER+）HER2-阴性（HER2-）乳腺癌细胞，elacestrant在诱导蛋白酶体介导的ERα蛋白降解的浓度下抑制17β-雌二醇介导的细胞增殖Elaestert在体外和体内显示出抗肿瘤活性，包括在ER+HER2-乳腺中对fulvestrant和cyclin-dependent kinase 4/6抑制剂耐药的癌症模型和那些含有fulvestlan和cyclin依赖性激酶4/6抑制剂的模型雌激素受体1基因（ESR1）突变。 01/2023 2023/2/1 sxz D0188 新增
Sacituzumab Govitecan-hziy 戈沙妥珠单抗 Trodelvy 拓达维 Immunomedics Inc 43943 FDA/NMPA TRODELVY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Locally Advanced or Metastatic Breast Cancer? Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. ? Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. Locally Advanced or Metastatic Urothelial Cancer ? Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. TRODELVY是一种Trop-2导向的抗体和拓扑异构酶抑制剂共轭物，适用于治疗患有以下疾病的成人患者：1.局部晚期或转移性乳腺癌。1）不可切除的局部晚期或转移性三阴性乳腺癌（mTNBC），之前接受过两种或更多的系统性治疗，其中至少有一种用于转移性疾病。2）不可切除的局部晚期或转移性激素受体（HR）阳性、人类表皮生长因子受体2（HER2）阴性（IHC 0、IHC 1+或IHC 2+/ISH-）乳腺癌，已接受内分泌治疗和至少两种额外的系统治疗的转移性疾病。2.局部晚期或转移性尿路上皮癌（mUC），既往接受过含铂化疗和程序性死亡受体-1（PD-1）或程序性死亡配体-1（PD-L1）抑制剂治疗。2022年，NMPA信息发布，戈沙妥珠单抗在国内获批，用于既往至少接受过2种系统治疗(其中至少一种治疗针对转移性疾病)的不可切除的局部晚期或转移性三阴性乳腺癌成人患者。 乳腺癌、尿路上皮癌 Sacituzumab govitecan-hziy is a Trop-2-directed antibody-drug conjugate. Sacituzumab is a humanized antibody that recognizes Trop-2. The small molecule, SN-38, is a topoisomerase I inhibitor, which is covalently attached to the antibody by a linker. Pharmacology data suggest that sacituzumab govitecan-hziy binds to Trop-2-expressing cancer cells and is internalized with the subsequent release of SN-38 via hydrolysis of the linker. SN-38 interacts with topoisomerase I and prevents re-ligation of topoisomerase I-induced single strand breaks. The resulting DNA damage leads to apoptosis and cell death. Sacituzumab govitecan-hziy decreased tumor growth in mouse xenograft models of triple-negative breast cancer. 戈沙妥珠单抗（Sacituzumab govitecan-hziy）是一种针对Trop-2的抗体-药物结合物。Sacituzumab是一种能识别Trop-2的人源化抗体。小分子SN-38是一种拓扑异构酶I抑制剂，它通过一个连接物与抗体共价连接。药理学数据表明，戈沙妥珠单抗与表达Trop-2的癌细胞结合并被内化，随后通过水解连接物释放SN-38。SN-38与拓扑异构酶I相互作用，阻止拓扑异构酶I诱导的单链断裂的重新连接。由此产生的DNA损伤会导致细胞凋亡和细胞死亡。戈沙妥珠单抗降低了三阴性乳腺癌小鼠异种移植模型的肿瘤生长。 02/2023 231007 pj D0190 适应症描述加句号 LXL
BBT-176 BBT-176, a novel, orally available fourth-generation EGFR TKI was designed to selectively and noncovalently inhibit triple-mutant EGFR 19Del/T790M/C797S and L858R/T790M/C797S at nanomolar concentrations. BBT-176是一种新型口服第四代表皮生长因子受体（EGFR）TKI，可在纳摩尔浓度下选择性地非共价抑制三重突变EGFR 19Del/T790M/C797S和L858R/T790M/C797S。 BBT-176是由BridgeBiotherapeutics公司开发的针对包括C797S在内的三重突变(Del19/T790M/C797S和L858R/T790M/C797S)的四代靶向药。临床前研究显示：BBT-176具有较强的抗肿瘤活性，特别是在动物模型中显示出明显的脑转移疗效。目前正在开展I/II期临床实验(NCT04820023)以观察BBT-176的安全性、耐受性和疗效。 231008 pj D0228 新增作用机制内容 LXL
QLH11811 QLH11811 is a new generation EGFR TKI designed to target the EGFR with ex19del/L858R/T790M/C797S mutations. QLH11811是新一代表皮生长因子受体（EGFR）TKI，旨在靶向ex19del/L858R/T790M/C797S突变的表皮生长因子受体。 QLH11811由齐鲁制药研发，对因EGFR C797S突变而导致奥希替尼耐药的NSCLC具有活性。临床前研究显示，QLH11811在野生型EGFR、激活突变ex19del以及多种组合型耐药突变中的活性均优于奥希替尼，并且针对L858R/C797S组合突变活性最高，在7种耐奥希替尼PDO模型显示了良好的抑制活性。 231008 pj D0229 新增作用机制内容 LXL
BPI-361175 BPI-361175 is a potent, selective, and orally bioavailable 4th generation EGFR-TKI which can potentially be used to treat NSCLC resistant mutations as well as at front line. BPI-361175 是一种强效、选择性和口服有效的第四代表皮生长因子受体（EGFR）-TKI，可用于治疗 NSCLC 耐药突变和一线治疗。 BPI-361175由贝达药业研发，主要治疗携带EGFR C797S突变及其他EGFR相关突变的晚期NSCLC等实体瘤。临床前数据显示：BPI-361175能有效抑制携带EGFR C797S突变肿瘤细胞的增殖，并在多个携带EGFR相关突变的移植瘤模型上展现了良好的抗肿瘤作用。目前也正在开展I期临床试验。 231008 pj D0230 新增作用机制内容 LXL
BLU-701 BLU-701 is a highly selective and potent investigational inhibitor of double-mutant EGFR, harboring the ex19del or L858R activating mutations and the C797S resistance mutation. BLU-701 是一种高选择性、强效的在研抑制剂，适用于携带 ex19del 或 L858R 激活突变和 C797S 耐药突变的 EGFR 双突变。 BLU-701由BlueprintMedicines公司研发，和BLU-945互为补充，对BLU-945抑制活性不强的单突变及双突变EGFR具有较强活性，特别是在临床前研究显示出显著的中枢神经系统渗透能力。目前正在开展I期临床试验(NCT05153408)。 231008 pj D0231 新增作用机制内容 LXL
Anvatabart Opadotin 重组人源化抗HER2单抗-AS269偶联物 Ambrx 乳腺癌 An antibody-drug conjugate (ADC) composed of anvatabart, a monoclonal antibody targeting human epidermal growth factor receptor 2 (EGFR2; HER2) site-specifically conjugated at two engineered residues of para-acetyl-phenylalanine (pAcF) via a stable oxime linker to the monomethyl auristatin F (MMAF) analog and potent microtubule inhibitor opadotin, with potential antineoplastic activity. Upon administration of anvatabart opadotin, the antibody moiety targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, opadotin binds to and inhibits tubulin polymerization, which results in G2/M phase arrest and tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. The site-specific conjugation of the cytotoxic agent to the antibody improves the biophysical properties of anvatabart opadotin, increases payload stability and optimizes its efficacy. Anvatabart Opadotin (ARX788) 是一种抗体药物共轭物（ADC）由针对人类表皮生长因子受体 2（EGFR2；HER2）的单克隆抗体 anvatabart 组成，该抗体通过稳定的肟连接体与单甲基澳瑞他汀 F（MMAF）类似物和强效微管抑制剂 opadotin 在两个对位乙酰基苯丙氨酸（pAcF）工程残基上特异性连接，具有潜在的抗肿瘤活性。服用ARX788后，抗体分子会靶向肿瘤细胞上的 HER2 并与之结合。抗体/抗原结合和内化后，opadotin与微管蛋白结合并抑制其聚合，从而导致 G2/M 期停滞和肿瘤细胞凋亡。HER2 是一种酪氨酸激酶受体，在许多癌细胞类型中过度表达。细胞毒剂与抗体的特异性位点共轭可改善ARX788的生物物理特性，提高有效载荷的稳定性并优化其药效。 ARX788是一种强效且高度稳定的抗体药物偶联物 (ADC)，与 T-DM1 作用机制类似，ARX788是由抗 HER2 单克隆抗体赫赛汀和细胞毒性小分子药物 AS269 组成的抗体偶联药物，抗 HER2 单克隆抗体可与人HER2特异性结合，AS269为高效微管抑制剂，可抑制细胞生长。ARX788与细胞表面HER2结合，通过内吞作用进入细胞，在溶酶体中被水解，释放出pAF-AS269（修饰氨基酸连接毒性分子），pAF-AS269结合微管，诱导细胞周期停滞及死亡。2020年12月FDA授予ARX788快速通道资格认定，作为单药用于已接受过一种或多种抗-HER2治疗的晚期或转移性HER2阳性乳腺癌患者。2021年1月FDA 授予ARX788胃癌孤儿药资格认定。2021年5月ARX788获中国CDE纳入突破性治疗品种，适应症为HER2阳性晚期乳腺癌二线治疗。ARX788针对HER2阳性乳腺癌患者的2期试验中国（ACE-Breast-02），全球（ACE-Breast-03），HER2 阳性胃癌/GEJ患者全球（ACE-Gastric-02）的2/3期试验正在开展。 231030 pj D0239 新增作用机制内容，新增中文名称
Tovorafenib 胶质瘤 Tovorafenib (TAK-580, MLN 2480) 是一种可口服的，具有选择性的广谱的 Raf 抑制剂。 Tovorafenib（DAY-101或TAK-580）是Day One Biopharmaceuticals公司开发的一种口服、脑穿透性pan-RAF激酶抑制剂，能够抑制野生型和某些突变形式的BRAF、CRAF和ARAF蛋白激酶。Tovorafenib已被美国食品和药物管理局（FDA）授予突破性治疗和罕见儿科疾病称号，用于治疗具有激活RAF改变的pLGG患者。Tovorafenib还获得了FDA授予的用于治疗恶性胶质瘤的孤儿药称号，以及欧盟委员会（EC）授予的用于治疗胶质瘤的孤儿药称号。 231008 pj D0240 新增作用机制内容 SXZ
BL-B01D1 百利天恒 非小细胞肺癌 BL-B01D1 is a first-in-class novel ADC consisting of an EGFRxHER3 bispecific antibody linked to a novel TOP-I inhibitor payload via a cleavable linker. BL-B01D1 是一种同类首创的新型 ADC，由 EGFRxHER3 双特异性抗体与新型 TOP-I 抑制剂有效载荷通过可裂解连接体连接而成。 BL-B01D1是百利天恒自主研发的世界上第一个，能够同时靶向EGFR和HER3的双抗ADC药物，可以实现针对EGFR依赖肿瘤的靶向杀伤，预防HER3引起的耐药，另外，还可以实现对肿瘤细胞的精确杀伤，减少小分子毒素对人体正常细胞的破坏。研究结果表明，本品整体安全性较好，未出现异常毒性反应，而人胰腺癌模型抗肿瘤活性优于第一三共HER3-ADC药物U3-1402。BL-B01D1目前正在进行临床试验。 231008 pj D0241 新增作用机制内容 SXZ
KL590586 科伦药业 实体瘤 KL590586 (A400/EP0031) is a potent next-generation selective RET inhibitor (SRI) with activity against acquired resistance mutations to first-generation SRIs, and brain metastases (mets). KL590586（A400/EP0031）是一种强效的新一代选择性RET抑制剂（SRI），对第一代SRI的获得性耐药突变和脑转移（mets）具有活性。 KL590586是一款新一代RET抑制剂，为靶向RET的小分子激酶抑制剂，靶点成熟，作用机制明确，拟用于RET融合或突变的晚期实体瘤的治疗。根据临床前研究的结果，KL590586有良好的抗肿瘤活性与安全性，且入脑性较好，有望在治疗脑肿瘤以及脑转移病灶方面发挥出色潜力。 231008 pj D0242 新增作用机制内容 SXZ
SY-5007 首药控股 非小细胞肺癌 SY-5007 is a highly potent RET inhibitor that selectively targets RET fusions and mutations. SY-5007 是一种高效的 RET 抑制剂，可选择性地针对 RET 融合和突变。 SY-5007是针对RET靶点首个进入临床阶段的国产创新药，也是目前临床进展最快的国产选择性RET抑制剂之一。SY-5007正在进行针对经过标准治疗后的RET阳性非小细胞肺癌（NSCLC）患者的关键性Ⅱ期临床试验，以及RET阳性甲状腺癌的Ⅱ期临床试验。 231008 pj D0243 新增作用机制内容 SXZ
HMPL-453 和记黄埔 恶性间皮瘤、肝内胆管癌 HMPL-453 is a novel, selective tyrosine kinase inhibitor against FGFR1, 2, and 3. HMPL-453 是一种新型的选择性酪氨酸激酶抑制剂，可抑制 FGFR1、2 和 3。 HMPL-453是一种新型、强效且高选择性的小分子FGFR 1、2和3抑制剂。在临床前研究中， HMPL-453较同类其他药物相比表现出更强的效力、更高的激酶选择性及更佳的安全性。在中国进行的HMPL-453 I期临床试验的剂量递增阶段已完成患者招募（NCT03160833）。在中国晚期恶性间皮瘤患者中进行的II期临床试验患者招募正在进行中（NCT04290325）。 231008 pj D0245 新增作用机制内容 SXZ
HS-10365 豪森药业 非小细胞肺癌 HS-10365 is a highly potent and selective tyrosine kinase inhibitor, and the preclinical studies have indicated its favorable safety and antitumor activity in RET-altered tumor models. HS-10365 是一种高效的选择性酪氨酸激酶抑制剂，临床前研究表明，它在 RET 突变的肿瘤模型中具有良好的安全性和抗肿瘤活性。 HS-10365是一种高效选择性酪氨酸激酶抑制剂，临床前研究表明其在RET改变的肿瘤模型中具有良好的安全性和抗肿瘤活性。目前，翰森制药已在国内启动并加速推进HS-10365针对晚期NSCLC患者的关键注册临床试验，同时评估HS-10365在RET异常的多种晚期实体瘤患者中的疗效和安全性。 231008 pj D0246 新增作用机制内容 SXZ
BBT-207 Bridge Biotherapeutics 非小细胞肺癌 BBT-207 is a reversible, mutant-specific, broad-spectrum TKI, active to clinically observed mutations of EGFR and is expected to be compatible with monotherapy of QD schedule in humans. BBT-207 是一种可逆的、突变特异性广谱 TKI，对临床观察到的表皮生长因子受体（EGFR）突变具有活性，预计可用于人体 QD 单药治疗。 BBT-207是一种广谱、高效的第4代EGFR TKI，对包括T790M和C797S在内的致敏和治疗出现的EGFR突变具有增强的活性。BBT-207有望增强EGFR突变NSCLC的治疗，无论是获得性耐药还是早期治疗，都具有治疗或预防中枢神经系统转移的潜力。首次针对携带EGFRm并曾接受EGFR-TKI治疗的患者的人体研究于2023年在美国开始登记。 231008 pj D0247 新增作用机制内容 SXZ
PLB1004 安达替尼 鞍石生物 非小细胞肺癌 PLB1004, a novel mono-anilino-pyrimidine small molecule inhibitor of EGFR, potently and irreversibly targets exon 20 insertion mutations with IC50 values ranging from 25.67-316.6 nM. PLB1004 是一种新型单苯胺基嘧啶小分子表皮生长因子受体抑制剂，能有效且不可逆地靶向 20 号外显子插入突变，IC50 值范围为 25.67-316.6 nM。 PLB1004（安达替尼）是中国原研、具有全球知识产权的表皮生长因子受体（EGFR）小分子抑制剂，拟治疗EGFR突变的晚期非小细胞肺癌。PLB1004在中国的I期临床研究开展后，2022年7月鞍石生物正式开启PLB1004的美国IND申报，开启了全球化进程。 231008 pj D0248 新增作用机制内容 SXZ
Trastuzumab Rezetecan 恒瑞医药 实体瘤 An antibody-drug conjugate (ADC) composed of trastuzumab, a humanized immunoglobulin G1-kappa (IgG1k) monoclonal antibody directed against the tumor-associated antigen (TAA) human epidermal growth factor receptor 2 (EGFR2; HER2; ErbB2) conjugated to rezetecan, which is composed of a cleavable linker and a camptothecin derivative, with potential antineoplastic activity. Upon administration of trastuzumab rezetecan, the trastuzumab moiety targets and binds to HER2 expressed on tumor cells. Upon cellular uptake and linker cleavage, the camptothecin derivative stabilizes covalent topoisomerase I-DNA complexes, and results in single-stranded and double-stranded DNA breaks, the inhibition of DNA replication, the induction of apoptosis and the inhibition of tumor cell proliferation in HER2-expressing tumor cells. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. Trastuzumab Rezetecan (SHR-A1811) 是一种抗体药物共轭物（ADC），由曲妥珠单抗（一种针对肿瘤相关抗原（TAA）人类表皮生长因子受体 2（EGFR2；HER2；ErbB2）的人源化免疫球蛋白 G1-κ（IgG1κ）单克隆抗体）与Rezetecan（由可裂解连接体和喜树碱衍生物组成）组成，具有潜在的抗肿瘤活性。服用Trastuzumab Rezetecan后，曲妥珠单抗分子会与肿瘤细胞上表达的 HER2 靶向结合。喜树碱衍生物被细胞吸收和连接体裂解后，可稳定共价拓扑异构酶 I-DNA 复合物，导致单链和双链 DNA 断裂，抑制 DNA 复制，诱导细胞凋亡，并抑制表达 HER2 的肿瘤细胞的增殖。HER2 是一种酪氨酸激酶受体，在许多癌细胞类型中过度表达。 SHR-A1811是恒瑞研发的新一代HER2 ADC，由人源化抗HER2单克隆抗体（曲妥珠单抗）、可裂解接头和DNA拓扑异构酶I抑制剂有效载荷组成，目前处于临床III期阶段。 231027 pj D0249 新增作用机制内容，更新药物名称
SY-3505 非小细胞肺癌 SY-3505 is a potent, brain-penetrant, 3rd-generation (gen) anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) with preclinical activity against both wild-type and most known resistance mutations of ALK occurring in 1st and 2nd-gen ALK TKI-resistant patients. SY-3505 (CT-3505) 是一种强效的脑穿透性第三代间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂（TKI），对第一代和第二代 ALK TKI 耐药患者中出现的 ALK 野生型和大多数已知的耐药突变具有临床前活性。 SY-3505是首药控股自主研发的国内首个进入临床试验的三代ALK抑制剂，它对野生型ALK和一代/二代药物关键耐药突变体蛋白激酶均具有非常强的抑制作用，在临床I期剂量递增阶段，SY-3505展现了良好的安全性，药物相关不良反应大多数为1-2级的轻微反应。SY-3505目前处于二期临床阶段，正在申请附条件获批上市资格。临床前研究显示SY-3505拥有超越现有二代ALK抑制剂的超强活性。 231008 pj D0253 新增作用机制内容 SXZ
Brimarefenib 百济神州 实体瘤 An orally available inhibitor of both monomer and dimer forms of activating mutations of the serine/threonine-protein kinase BRAF (B-raf) protein, including V600 BRAF mutations, non-V600 BRAF mutations, and RAF fusions, with potential antineoplastic activity. Upon administration, BRAF inhibitor BGB-3245 targets and binds to both monomeric and dimeric forms of activating BRAF mutations and fusions. This may result in the inhibition of BRAF-mediated signaling and inhibit proliferation in tumor cells expressing BRAF mutations and fusions. BRAF belongs to the RAF family of serine/threonine protein kinases and plays a role in regulating the mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) signaling pathway, which is often dysregulated in human cancers and plays a key role in tumor cell proliferation and survival. BRAF mutations and fusions have been identified in a number of solid tumors and are drivers of cancer growth. Brimarefenib (BGB-3245) 是一种口服抑制剂，可抑制丝氨酸/苏氨酸蛋白激酶 BRAF（B-raf）蛋白活化突变的单体和二聚体形式，包括 BRAF V600 突变、非 BRAF V600 突变和 RAF 融合，具有潜在的抗肿瘤活性。给药后，BRAF 抑制剂 BGB-3245 可靶向并结合活化型 BRAF 突变和融合的单体和二聚体形式。这可能会抑制 BRAF 介导的信号传导，并抑制表达 BRAF 突变和融合的肿瘤细胞的增殖。BRAF属于丝氨酸/苏氨酸蛋白激酶RAF家族，在调节丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）信号通路中发挥作用。在一些实体瘤中发现了 BRAF 突变和融合，它们是癌症生长的驱动因素。 BGB-3245是MapKure、百济神州和SpringWorks Therapeutics共同拥有的一款RAF抑制剂，针对包括BRAF V600突变型、BRAF非V600突变型和RAF融合在内的单聚体和二聚体BRAF激活突变。这些突变在包括非小细胞肺癌（NSCLC）、结直肠癌（CRC）、甲状腺癌及脑肿瘤的多项实体瘤中被证实是肿瘤生长的驱动因素。临床前数据表明，BGB-3245在现已获批BRAF抑制剂无法作用的BRAF融合和非V600突变型的推动下，在患者衍生的异种移植物中具有活性。此外，BGB-3245在临床前肿瘤模型中针对V600 BRAF突变的活动也表明其成为这类患者潜在的治疗方案来降低二聚体驱动的耐药性。除了作为单药治疗多项基因变异导致的实体瘤之外，BGB-3245有望在未来用于合理的联合疗法。 231009 pj D0271 更新英文名称
DB-1310 映恩生物 实体瘤 DB-1310 is a HER3 ADC composed of a novel humanized anti-Her3 immunoglobulin G1 (IgG1) monoclonal antibody, covalently linked to a proprietary DNA topoisomerase I inhibitor payload via a maleimide tetrapeptide-based cleavable linker with a drug antibody ratio (DAR) of approximately eight. DB-1310 是一种 HER3 ADC，由新型人源化抗 HER3 免疫球蛋白 G1 (IgG1) 单克隆抗体，通过马来酰亚胺四肽可裂解连接子与专有的 DNA 拓扑异构酶I抑制剂有效载荷共价连接组成，药物抗体比 (DAR) 约为 8。 DB-1310是映恩生物基于其DITAC技术平台开发的靶向HER3的ADC产品，由新型人源化抗Her3单克隆抗体通过马来酰亚胺可裂解linker与专有的DNA拓扑异构酶I抑制剂共价连接，DAR值约为8。今年AACR大会上，根据映恩生物公布的最新临床前研究中显示，DB-1310表现出优于U3-1402的肿瘤抑制效果和安全性；并且在与EGFR小分子抑制剂联合治疗中表现出优秀的协调治疗效果。今年5月24日，据CDE官网公示，映恩生物的HER3 ADC药物“注射用DB-1310”临床试验申请获得临床试验默示许可（受理号：CXSL2300200），拟用于治疗晚期/转移性实体瘤。 231008 pj D0272 新增作用机制内容 SXZ
MRG003 乐普生物 实体瘤 An antibody-drug conjugate (ADC) consisting of a human immunoglobulin G1 (IgG1) monoclonal antibody directed against the epidermal growth factor receptor (EGFR) conjugated to monomethyl auristatin E (MMAE), an auristatin derivative and potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration of anti-EGFR ADC MRG003, the monoclonal antibody moiety binds to EGFR on tumor cell surfaces. Following receptor internalization, the MMAE moiety is released and binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and apoptosis. This inhibits the proliferation of EGFR-expressing tumor cells. EGFR, overexpressed by a variety of cancers, plays a key role in tumor cell proliferation and survival. MRG003 是一种抗体药物共轭物（ADC），由针对表皮生长因子受体（EGFR）的人免疫球蛋白 G1（IgG1）单克隆抗体与单甲基澳瑞他汀 E（MMAE）（一种金丝桃素衍生物和强效微管干扰剂）共轭组成，具有潜在的抗肿瘤活性。服用抗EGFR ADC MRG003 后，单克隆抗体分子会与肿瘤细胞表面的EGFR结合。受体内化后，MMAE 分子释放出来，与微管蛋白结合并抑制其聚合，从而导致 G2/M 期停滞和细胞凋亡。这就抑制了表达EGFR的肿瘤细胞的增殖。EGFR在多种癌症中过度表达，在肿瘤细胞的增殖和存活中起着关键作用。目前，MRG003 已获得NMPA的突破性治疗认定（BTD），用于治疗既往经至少二线系统化疗（包括含铂化疗）和PD-1（L1）治疗失败的复发/转移性鼻咽癌。 MRG003是一款靶向EGFR的ADC，它由EGFR靶向单抗与强效的微管抑制剂MMAE分子通过vc链接体偶联而成。此前，乐普生物曾披露MRG003的I期非随机临床研究（登记号：NCT04868344）数据，结果表明：MRG003治疗晚期实体瘤患者具有可控的安全性，且表现出对EGFR阳性晚期头颈部鳞状细胞癌和鼻咽癌的良好抗肿瘤活性。目前，NMPA已将MRG003纳入突破性疗法，用于既往经至少二线系统化疗（包括含铂化疗）和PD-1（L1）治疗失败的复发/转移性鼻咽癌。MRG003于2017年8月在国内首次获批临床，并于次年3月首次公示临床试验。当前正在开展针对鼻咽癌、胃癌、胆道癌等多个癌种的 II 期临床试验。 231008 pj D0274 新增作用机制内容 SXZ
LBL-033 维立志博 实体瘤 LBL-033, a novel bispecific antibody targeting CD3 and MUC16 with a unique epitope, which is located at the MUC16 membrane-proximal domain, with affinity differentiation between anti-MUC16 and anti-CD3. It is shown a great anti-tumor efficacy in animal models, with a good safety profile in monkeys. LBL-033是一种靶向CD3和MUC16的新型双特异性抗体，其独特的表位位于MUC16的膜近端结构域，具有抗MUC16和抗CD3的亲和性。该抗体在动物模型中具有很好的抗肿瘤疗效，在猴子体内具有良好的安全性。 2023年6月12日，FDA官网显示，维立志博1类生物制品注射用LBL-033获批Ⅰ/Ⅱ期临床，拟用于治疗卵巢癌等恶性肿瘤。LBL-033是一种抗MUC16/CD3双特异抗体，可同时靶向表达MUC16的肿瘤细胞和表达CD3的T细胞。该药此前已经在中国获批临床，并于2023年4月在中山大学肿瘤防治中心完成首例受试者给药。 231008 pj D0277 新增作用机制内容 SXZ
Trastuzumab Botidotin 舒泰来 科伦博泰 乳腺癌 An antibody-drug conjugate (ADC) composed of trastuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (EGFR2; HER2; ErbB2), conjugated, via a cleavable linker, to the microtubule inhibitor and auristatin derivative duostatin-5 (Duo-5), with potential antineoplastic activity. Upon administration of trastuzumab botidotin, the trastuzumab moiety targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, duo-5 binds to tubulin and inhibits its polymerization, which results in cell cycle arrest and induces tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. Trastuzumab Botidotin (A166) 是一种抗体药物共轭物（ADC），由曲妥珠单抗（一种靶向人类表皮生长因子受体 2 [EGFR2；HER2；ErbB2]的人源化单克隆抗体）与微管抑制剂和澳瑞他汀衍生物 duostatin-5 (Duo-5)通过可裂解连接体共轭而成，具有潜在的抗肿瘤活性。服用A166后，曲妥珠单抗分子会靶向肿瘤细胞上的 HER2 并与之结合。抗体/抗原结合和内化后，duo-5 会与微管蛋白结合并抑制其聚合，从而导致细胞周期停滞并诱导肿瘤细胞凋亡。HER2 是一种酪氨酸激酶受体，在许多癌细胞类型中过度表达。 注射用A166（商品名：舒泰来）是科伦博泰研发的靶向HER2的创新ADC产品。它能够靶向HER2表达的肿瘤细胞，通过内吞进入细胞后，在胞内溶酶体中切割并释放毒素分子高效杀伤肿瘤细胞，兼具抗体药物的靶向性以及传统化疗药物的高杀伤性等特点。中国药物临床试验登记与信息公示平台官网公示，科伦博泰已经在中国启动一项3期临床研究，评估注射用A166对比注射用恩美曲妥珠单抗（T-DM1）治疗既往接受过曲妥珠单抗和紫杉类治疗的HER2阳性不可切除或转移性乳腺癌患者的有效性和安全性。公开资料显示，A166是一款靶向HER2的创新抗体偶联药物（ADC），已经于今年5月在中国递交上市申请，拟定适应症为既往经二线及以上抗HER2治疗失败的HER2阳性不可切除的局部晚期、复发或转移性乳腺癌。 231030 pj D0278 新增作用机制内容，更新药物名称 SXZ
SKB264 科伦博泰 非小细胞肺癌、三阴性乳腺癌、实体瘤 SKB264 is a novel anti-TROP2 ADC developed using sulfonyl pyrimidine-CL2A-carbonate linker to conjugate its payload, a belotecan-derivative topoisomerase I inhibitor, to achieve an average Drug-to-antibody Ratio (DAR) of 7.4. SKB264是一种新型抗TROP2 ADC，采用磺酰嘧啶-CL2A-碳酸酯连接体与有效载荷（贝洛替康衍生物拓扑异构酶I抑制剂）共轭，平均药物抗体比（DAR）为7.4。 SKB264是由科伦博泰拥有自主知识产权的靶向TROP2的人源化单克隆抗体、可酶促裂解的Linker和新型拓扑异构酶I抑制剂组合而成的新一代抗体偶联药物(ADC)，结合了单抗对肿瘤细胞表面靶抗原的特异性和细胞毒性药物的高效性。基于初步临床数据，SKB264目前正在开展针对多个瘤种的单药/联用的II期和III期临床试验。 231008 pj D0279 新增作用机制内容 SXZ
Opnurasib 诺华 非小细胞肺癌 Opnurasib (JDQ-443; NVP-JDQ443) 是一种口服有效和选择性的共价 KRAS G12C 抑制剂。Opnurasib 具有抗肿瘤活性。 JDQ443是诺华公司目前在研的口服KRAS G12C抑制剂，JDQ443与现有的Sotorasib和Adagrasib相比有着更优的结构特点。JDQ443在以共价、不可逆的结合模式占据KRAS G12C蛋白的Switch II环的基础上，有着全新的结合模式直达C12残基，且能避免与耐药相关的H95残基发生直接相互作用，进而使得KRAS G12C“锁定”在失活状态，抑制了肿瘤中该通路的过度活化。在临床前研究中，JDQ443已显示出对KRAS G12C细胞信号通路及细胞增殖的强效抑制，并具有剂量依赖性的抗肿瘤活性。 231008 pj D0282 新增作用机制内容，新增中文名称(NCI有相关说明：Opnurasib (An inhibitor of the oncogenic KRAS substitution mutation, G12C, with potential antineoplastic activity. Upon administration, opnurasib selectively targets the KRAS G12C mutant and inhibits KRAS G12C mutant-dependent signaling. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis.) SXZ
APG-2449 亚盛医药 非小细胞肺癌、卵巢癌、实体瘤 FAK/ALK/ROS1 Inhibitor APG-2449 is an orally available kinase inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), focal adhesion kinase (FAK) and the receptor tyrosine kinase C-ros oncogene 1 (ROS1), with potential antineoplastic activity. Upon administration, ALK/FAK/ROS1 inhibitor APG-2449 selectively binds to and inhibits ALK, FAK and ROS1 kinases. The inhibition leads to disruption of ALK-, FAK- and ROS1-mediated signal transduction pathways and eventually inhibits tumor cell growth in ALK-, FAK- and ROS1-overexpressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; its dysregulation and gene rearrangements are associated with a variety of tumors. The cytoplasmic tyrosine kinase FAK, a signal transducer for integrins, is upregulated and constitutively activated in various tumor types; it plays a key role in tumor cell migration, proliferation, survival, and tumor angiogenesis. ROS1, overexpressed in certain cancer cells, plays a key role in cell growth and survival of cancer cells. APG-2449 是一种可口服的受体酪氨酸激酶间变性淋巴瘤激酶（ALK）、粘着斑激酶（FAK）和受体酪氨酸激酶C-ros癌基因1（ROS1）激酶抑制剂，具有潜在的抗肿瘤活性。给药后，APG-2449 可选择性地结合并抑制 ALK、FAK 和 ROS1 激酶。抑制作用会破坏 ALK、FAK 和 ROS1 介导的信号转导通路，最终抑制 ALK、FAK 和 ROS1 基因表达肿瘤细胞的生长。ALK 属于胰岛素受体超家族，在神经系统发育过程中发挥着重要作用；它的失调和基因重排与多种肿瘤有关。细胞质酪氨酸激酶 FAK 是整合素的信号转导子，在多种肿瘤中上调并组成性激活，在肿瘤细胞迁移、增殖、存活和肿瘤血管生成中发挥关键作用。ROS1 在某些癌细胞中过度表达，在癌细胞的生长和存活中起着关键作用。 APG-2449为亚盛医药自主研发的全新的、具有口服活性的小分子FAK/ALK/ROS1三联TKI，为首个进入临床阶段的本土原研的第三代ALK抑制剂。APG-2449治疗NSCLC的临床数据表明该品种有望通过抑制FAK，为NSCLC患者提供一个可有效克服耐药的全新治疗策略。数据表明，APG-2449在NSCLC患者中具有良好的疗效和安全性，在28例经二代ALK TKI 治疗失败的患者中，观察到8例部分缓解（PR）。 231008 pj D0283 新增作用机制内容 SXZ
BI-1810631 勃林格殷格翰 非小细胞肺癌 An orally bioavailable inhibitor of the receptor tyrosine kinase human epidermal growth factor receptor 2 (HER2; ErbB2; HER-2), with potential antineoplastic activity. Upon oral administration, HER2 inhibitor BI 1810631 covalently binds to and inhibits the activity of both wild-type and HER2 mutants, including HER2 mutants with exon 20 insertion (ex20ins) mutations. This prevents HER2-mediated signaling and may lead to cell death in HER2-expressing tumor cells. HER2, a receptor tyrosine kinase overexpressed on a variety of tumor cell types, plays an important role in tumor cell proliferation and tumor vascularization. BI-1810631 是一种可口服的受体酪氨酸激酶人表皮生长因子受体 2（HER2；ErbB2；HER-2）抑制剂，具有潜在的抗肿瘤活性。口服给药后，HER2 抑制剂 BI 1810631 可与野生型和 HER2 突变体共价结合并抑制其活性，包括具有外显子 20 插入（ex20ins）突变的 HER2 突变。这能阻止 HER2 介导的信号传导，并可能导致表达 HER2 的肿瘤细胞死亡。HER2是一种在多种肿瘤细胞类型中过度表达的受体酪氨酸激酶，在肿瘤细胞增殖和肿瘤血管形成中发挥着重要作用。 BI-1810631是勃林格殷格翰在研的一种新型选择性口服小分子抑制剂，其选择性抑制HER2而不影响野生型EGFR；临床前数据显示其对HER2突变均具有强效的抑制活性，同时可有效避免EGFR相关的剂量限制性毒性。Beamion Lung 1是一项正在进行的Ia/Ib期临床研究，从2023年ASCO公布的Ia期最新数据来看，BI-1810631单药治疗在HER2突变的NSCLC中显示出了非常不错的治疗效果，同时具备较好的安全性数据。 231009 pj D0295 新增作用机制内容 SXZ
TQB2930 中国生物制药 乳腺癌 A bispecific antibody directed against two distinct domains of the tumor-associated antigen (TAA) human tyrosine kinase receptor epidermal growth factor receptor 2 (HER2; ErbB2; HER-2), with potential immunomodulating and antineoplastic activities. Upon administration, anti-HER2 bispecific antibody TQB2930 simultaneously targets and binds to two different domains of HER2. This prevents the activation of HER2 signaling pathways, resulting in tumor cell apoptosis and growth inhibition of HER2-expressing tumor cells. HER2, overexpressed on a variety of tumor cell types, plays an important role in tumor cell proliferation, differentiation and survival. TQB2930 是一种针对肿瘤相关抗原（TAA）人类酪氨酸激酶受体表皮生长因子受体 2（HER2；ErbB2；HER-2）两个不同结构域的双特异性抗体，具有潜在的免疫调节和抗肿瘤活性。给药后，抗 HER2 双特异性抗体 TQB2930 可同时靶向并结合 HER2 的两个不同结构域。这将阻止 HER2 信号通路的激活，从而导致肿瘤细胞凋亡并抑制表达 HER2 的肿瘤细胞的生长。HER2 在多种肿瘤细胞类型中过度表达，在肿瘤细胞增殖、分化和存活过程中发挥着重要作用。 资料显示，TQB2930是一种靶向实体肿瘤细胞的双特异抗体，实现了针对两个靶点的协同增效作用。其能够阻断肿瘤生长的驱动基因信号，并通过多种机制杀伤肿瘤细胞。临床前药效试验显示该分子能够显著抑制肿瘤生长。 231009 pj D0297 新增作用机制内容 SXZ
Enfortumab Vedotin 维恩妥尤单抗 Padcev 安斯泰来 43817 FDA PADCEV is a Nectin-4-directed antibody and microtubule inhibitor conjugate indicated:? as a single agent for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum?containing chemotherapy, or are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy. in combination with pembrolizumab for the treatment of adult patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy. PADCEV是一种Nectin-4导向的抗体和微管抑制剂结合物，适用于：-作为单药治疗局部晚期或转移性尿路上皮癌的成年患者，这些患者之前接受过程序性死亡受体-1（PD-1）或程序性死亡配体-1（PD-L1）抑制剂和含铂化疗，或不符合含顺铂化疗的条件，且之前接受过一种或多种治疗。- 与pembrolizumab联合治疗不符合含顺铂化疗条件的局部晚期或转移性尿路上皮癌成年患者。 尿路上皮癌 Enfortumab vedotin-ejfv is an ADC. The antibody is a human IgG1 directed against Nectin-4, an adhesion protein located on the surface of cells. The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease-cleavable linker. Nonclinical data suggest that the anticancer activity of enfortumab vedotin-ejfv is due to the binding of the ADC to Nectin-4-expressing cells, followed by internalization of the ADC-Nectin-4 complex, and the release of MMAE via proteolytic cleavage. Release of MMAE disrupts the microtubule network within the cell, subsequently inducing cell cycle arrest and apoptosis. The combination of enfortumab vedotin-ejfv with a PD-1 blocking antibody resulted in up-regulation of immune function and increased anti-tumor activity in syngeneic mouse tumor models expressing Nectin-4. Enfortumab vedotin-ejfv是一种ADC药物。该抗体是一种针对Nectin-4的人类IgG1，Nectin-4是一种位于细胞表面的粘附蛋白。小分子MMAE是一种微管破坏剂，通过一种可被蛋白酶清除的连接剂与抗体相连。非临床数据表明，enfortumab vedotin-ejfv的抗癌活性是由于ADC与表达Nectin-4的细胞结合，随后ADC-Nectin-4复合物内化，并通过蛋白酶裂解释放MMAE。MMAE的释放破坏了细胞内的微管网络，随后诱发细胞周期停滞和凋亡。enfortumab vedotin-ejfv与PD-1阻断抗体联合使用，在表达Nectin-4的合成小鼠肿瘤模型中，免疫功能得到上调，抗肿瘤活性增强。 04/2023 231031 pj D0298 新增药物中文名称 SXZ
ZN-A-1041 赞荣医药 乳腺癌 An orally bioavailable inhibitor of the receptor tyrosine kinase human epidermal growth factor receptor 2 (HER2; ErbB2; HER-2), with potential antineoplastic activity. Upon oral administration, HER2 inhibitor ZN-A-1041 selectively binds to and inhibits the activity of HER2. This prevents HER2-mediated signaling and may lead to cell death in HER2-expressing tumor cells. HER2, a receptor tyrosine kinase overexpressed on a variety of tumor cell types, plays an important role in tumor cell proliferation and tumor vascularization. ZN-A-1041是一种口服生物活性受体酪氨酸激酶人表皮生长因子受体 2（HER2；ErbB2；HER-2）抑制剂，具有潜在的抗肿瘤活性。口服 HER2 抑制剂 ZN-A-1041 可选择性地与 HER2 结合并抑制其活性。这将阻止 HER2 介导的信号传导，并可能导致表达 HER2 的肿瘤细胞死亡。HER2是一种在多种肿瘤细胞中过度表达的受体酪氨酸激酶，在肿瘤细胞增殖和肿瘤血管形成中发挥着重要作用。 ZN-A-1041是一款同类最佳的HER2口服选择性酪氨酸激酶抑制剂，用于治疗HER2阳性乳腺癌脑转移的患者以及预防脑转移的发生。ZN-A-1041的主要特点在于：（1）具备高度血脑屏障通透性，因此可潜在用于治疗HER2阳性乳腺癌脑转移的患者以及预防脑转移的发生。高达50%的HER2阳性转移性乳腺癌患者在病程中会发生脑转移；（2）相对其他TKI不良反应较少，且在联合治疗中使用足够安全；（3）在对大分子药物无反应或最小反应的患者中具有治疗活性，且口服药物给药方便。 231008 pj D0299 新增作用机制内容 SXZ
BB-1701 百力司康 实体瘤 BB-1701 is an antibody-drug conjugate consisting of a humanized IgG1κ monoclonal antibody and eribulin. When BB-1701 targets HER2-expressing cancer cells and is internalized, free eribulin is cleaved from the ADC by cathepsin b and causes cytotoxicity to cancer cells. The neighboring cells were affected with bystander effects, like cytotoxicity on tumor cells and non-cytotoxic effects on microenvironment by free eribulin. BB-1701 是一种抗体-药物共轭物（ADC），由人源化 IgG1κ 单克隆抗体和艾立布林组成。当 BB-1701 靶向表达 HER2 的癌细胞并被内化时，游离的艾立布林会被组织蛋白酶 b 从 ADC 中裂解，从而对癌细胞产生细胞毒性。邻近细胞则受到旁观者效应的影响，如游离艾立布林对肿瘤细胞的细胞毒性和对微环境的非细胞毒性效应。 BB-1701是由百力司康开发的HER2 ADC，由抗HER2 IgG1κ抗体和Eribulin结合而成，具有旁观者效应和免疫性细胞死亡（ICD）活性。 231008 pj D0300 新增作用机制内容 SXZ
Entinostat 恩替诺特 拜耳 乳腺癌 Entinostat 选择性，可口服的 HDAC class I 抑制剂，抑制 HDAC1，HDAC2 和 HDAC3 的 IC50 分别为 243 nM，453 nM 和 248 nM。 Entinostat（恩替诺特，AbMole #M1791）是一种合成的苯酰胺衍生物组蛋白去乙酰化酶 (HDAC) 抑制剂，可以选择性地抑制 I 类、II类和 III类 HDAC 酶。这种作用会促进组蛋白超乙酰化和特定基因的转录激活，从而抑制细胞增殖、提高细胞分化并诱导细胞凋亡。恩替诺特通过降低 BRCA1 表达和阻滞 DNA 复制叉进展来抑制 DNA 损伤修复系统，并形成难以修复的 DNA 损伤，最终导致细胞死亡。 231008 pj D0306 新增作用机制内容 SXZ
ABBV-400 艾伯维 实体瘤 An antibody-drug conjugate (ADC) composed of a monoclonal antibody against the tumor-associated antigen (TAA) proto-oncogene c-Met (hepatocyte growth factor receptor; HGFR) linked to an undisclosed topoisomerase inhibitor, with potential antineoplastic activity. Upon intravenous administration of anti-c-Met ADC ABBV-400, the monoclonal antibody moiety targets and binds to c-Met expressed on tumor cells. Upon binding and internalization, the topoisomerase inhibitor is released, which binds to and inhibits topoisomerase, thereby inhibiting DNA replication and killing the c-Met-expressing cancer cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis and tumor angiogenesis. ABBV-400 是一种抗体药物共轭物（ADC），由抗肿瘤相关抗原（TAA）原癌基因 c-Met（肝细胞生长因子受体；HGFR）的单克隆抗体与一种未公开的拓扑异构酶抑制剂连接而成，具有潜在的抗肿瘤活性。静脉注射抗 c-Met ADC ABBV-400 后，单克隆抗体分子会靶向并结合肿瘤细胞上表达的 c-Met。c-Met 是一种受体酪氨酸激酶，在许多肿瘤细胞类型中过度表达或突变，在肿瘤细胞增殖、生存、侵袭、转移和肿瘤血管生成中起着关键作用。 ABBV-400是艾伯维的下一代c-Met药物，payload用了topoisomerase inhibitor，主要针对cMET表达量在中~高水平的患者，对表达量低的患者毒性增加。利用c-Met向过度表达的肿瘤细胞提供拓扑异构酶抑制剂，抑制DNA复制，从而阻止细胞增殖并诱发细胞毒性。目前，ABBV-400已进展到临床I期试验（NCT05029882），主要目的是评估ABBV-400治疗晚期实体肿瘤成年患者时的不良事件和疾病活动变化。试验包括剂量扩增和剂量扩展阶段，剂量扩增阶段治疗组接受不同剂量的ABBV-400，以探索推荐的第二阶段剂量（RP2D）。 231009 pj D0307 新增作用机制内容 SXZ
HS-20093 翰森制药 实体瘤 An antibody-drug conjugate (ADC) composed of a human immunoglobulin (Ig) G1 monoclonal antibody directed against the T-cell checkpoint ligand B7-homologue 3 (B7-H3, CD276) linked to an as of yet undefined cytotoxic agent, with potential antineoplastic activity. Upon administration of anti-B7-H3 ADC HS-20093, the anti-B7-H3 monoclonal antibody moiety targets and binds to B7-H3 expressed on tumor cells. Upon binding, internalization and linker cleavage, the cytotoxic agent is release and induces apoptosis specifically in B7-H3-expressing tumor cells through an as of yet undefined mechanism of action (MoA). B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is an immunoregulatory protein overexpressed on certain tumor cell types and on various immune cells. It is a negative regulator of the T-cell activation and its overexpression plays a key role in tumor cell invasion and metastasis. HS-20093 是一种抗体-药物共轭物（ADC），由针对 T 细胞检查点配体 B7-同源物 3（B7-H3，CD276）的人类免疫球蛋白（Ig）G1 单克隆抗体与一种尚未确定的细胞毒剂连接而成，具有潜在的抗肿瘤活性。服用抗 B7-H3 ADC HS-20093 后，抗 B7-H3 单克隆抗体分子会靶向并结合肿瘤细胞上表达的 B7-H3。结合、内化和连接体裂解后，细胞毒剂释放出来，并通过尚未明确的作用机制（MoA）诱导表达 B7-H3 的肿瘤细胞凋亡。B7-H3 是一种 I 型跨膜蛋白，属于 B7 协同刺激蛋白超家族，是一种在某些肿瘤细胞类型和各种免疫细胞上过度表达的免疫调节蛋白。它是 T 细胞活化的负调控因子，其过度表达在肿瘤细胞侵袭和转移中起着关键作用。 HS-20093是翰森制药进展最快的ADC，目前已进入2期临床。2023 ASCO上公布的HS-20093治疗晚期实体瘤的多中心、开放标签1期临床试验结果显示：无论基线B7-H3表达水平如何，在40例可评估治疗反应的患者中，在接受HS-20093从4.0 mg/kg到12.0 mg/kg剂量治疗的患者中，观察到14例部分缓解（PR），疾病控制率为85.0%。 231009 pj D0309 新增作用机制内容 SXZ
SGN-B6A Seagen 实体瘤 An antibody-drug conjugate (ADC) composed of a humanized antibody targeting integrin beta-6 and conjugated to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, the antibody moiety of anti-integrin beta-6/MMAE ADC SGN-B6A targets and binds to integrin beta-6 on the surface of tumor cells. Following internalization of SGN-B6A and release of MMAE, MMAE targets and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in integrin beta-6-expressing tumor cells. Integrin beta-6 is a subunit of integrin alpha-V beta-6 (aVb6). Integrin aVb6, a cell adhesion and signaling receptor, is upregulated in certain cancer cell types and has been associated with increased proliferation, migration and invasion of tumor cells. SGN-B6A 是一种抗体-药物共轭物（ADC），由靶向整合素 β-6 的人源化抗体和具有潜在抗肿瘤活性的微管破坏细胞毒剂单甲基澳瑞他汀 E（MMAE）共轭而成。给药后，抗整合素 β-6/MMAE ADC SGN-B6A 的抗体分子会靶向肿瘤细胞表面的整合素 β-6 并与之结合。SGN-B6A 内化并释放出 MMAE 后，MMAE 靶向并与微管蛋白结合，抑制微管聚合。这将导致表达整合素 β-6 的肿瘤细胞进入 G2/M 期细胞周期并凋亡。整合素 β-6 是整合素 α-V β-6（αVβ6）的一个亚基。整合素 αVβ6 是一种细胞粘附和信号受体，在某些癌细胞类型中上调，并与肿瘤细胞的增殖、迁移和侵袭增加有关。 SGN-B6A是一款靶向整合素β的新型ADC药物，已在针对非小细胞肺癌的临床前研究中显示出广泛的抗肿瘤活性，并在整合素β高表达模型中显示出最佳反应。 231009 pj D0312 新增作用机制内容 SXZ
TORL-1-23 TORL BioTherapeutics 实体瘤 An antibody-drug conjugate (ADC) composed of a monoclonal antibody against an unnamed tumor-associated antigen (TAA) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of TORL-1-23 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an as of yet unknown mechanism of action. TORL-1-23 是一种抗体-药物共轭物（ADC），由抗未命名的肿瘤相关抗原（TAA）的单克隆抗体与一种尚未公开的细胞毒剂连接而成，具有潜在的抗肿瘤活性。静脉注射后，TORL-1-23 的单克隆抗体分子会靶向并结合肿瘤细胞上表达的 TAA。结合和内化后，细胞毒剂会释放出来，并通过一种目前尚不清楚的作用机制杀死表达 TAA 的癌细胞。 TORL-1-23是一款由抗CLDN6单抗与微管蛋白抑制剂MMAE通过可切割连接子偶联生成的ADC。它具有高度选择性，在体外实验中，TORL-1-23显示出对过度表达CLDN6的细胞系的强力和特异性结合，而不结合到过度表达其他claudin蛋白的细胞系，如CLDN3，CLDN4和CLDN9。 231009 pj D0315 新增作用机制内容 SXZ
ZB131 Zielbio 实体瘤 A humanized monoclonal antibody directed against human plectin (plectin-1; plectin 1), with potential antineoplastic activity. Upon administration, anti-plectin monoclonal antibody ZB131 specifically binds to plectin expressed on the cell surface of cancer cells, thereby activating the immune system to induce an anti-tumor T-cell response against plectin-expressing cancer cells and inducing apoptosis in these cancer cells. Plectin, a pro-tumorigenic protein, is normally found inside the cytoplasm of healthy cells but is only selectively expressed on the cell surface of various cancer cells. Cancer-specific plectin (CSP), also known as cell surface plectin-1 (CSP1), plays an important role in cancer cell proliferation, migration and invasion. ZB131 是一种针对人类 plectin（plectin-1；plectin 1）的人源化单克隆抗体，具有潜在的抗肿瘤活性。给药后，抗 plectin 单克隆抗体 ZB131 能与癌细胞细胞表面表达的 plectin 特异性结合，从而激活免疫系统，诱导针对表达 plectin 的癌细胞的抗肿瘤 T 细胞反应，并诱导这些癌细胞凋亡。Plectin 是一种促肿瘤蛋白，通常存在于健康细胞的细胞质内，但只选择性地表达在各种癌细胞的细胞表面。癌症特异性 Plectin（CSP），又称细胞表面 Plectin-1（CSP1），在癌细胞增殖、迁移和侵袭过程中发挥着重要作用。 ZB131是一种对肿瘤特异性凝集素具有高亲和力和特异性的单克隆抗体，针对在多种恶性肿瘤中发现的与侵袭性肿瘤和不良预后有关的癌症特异性凝集素（CSP）。ZB131在临床前研究中显示出与CSP的高度特异性结合和强大的抗癌活性。一项1期/2期试验正在进行中，以研究ZB131在实体瘤（包括胆管癌，胰腺癌和卵巢癌）患者中的安全性，耐受性和有效性，FDA授予ZB131用于治疗胆管癌的孤儿药资格。 231009 pj D0316 新增作用机制内容 SXZ
CBX-12 Cybrexa 实体瘤 A conjugate composed of a pH low insertion peptide (pHLIP) linked to the camptothecin analog exatecan, with potential antineoplastic activity. Upon administration of pHLIP-exatecan conjugate CBX-12, the pHLIP moiety specifically targets and gets inserted into the cellular membrane of tumor cells in environments with low extracellular pH. Then the exatecan moiety is released intracellularly via glutathione reduction of the linker. Exatecan inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. Tumor cell environments are more acidic than normal, healthy tissue environments. The pHLIP forms an alpha helix and becomes inserted across the cell membrane specifically at the low extracellular pH found within tumors. CBX-12 是一种由低pH插入肽（pHLIP）与喜树碱类似物依喜替康（exatecan）连接而成的共轭物，具有潜在的抗肿瘤活性。服用 pHLIP-依喜替康共轭物 CBX-12 后，pHLIP 分子会在细胞外 pH 值较低的环境中特异性地靶向并插入肿瘤细胞的细胞膜。然后，依喜替康分子通过谷胱甘肽还原连接体在细胞内释放。依喜替康会抑制 DNA 拓扑异构酶 I 的活性，从而抑制 DNA 复制，导致细胞周期停滞和肿瘤细胞凋亡。与正常的健康组织环境相比，肿瘤细胞环境的酸性更强。pHLIP 形成一个α螺旋，在肿瘤细胞内细胞外 pH 值较低的情况下，会穿过细胞膜插入细胞内。 CBX-12是一种处于first-in-class的多肽偶联药物（PDC），利用Cybrexa的专有的alphalex技术，将exatecan(一种高效的第二代拓扑异构酶I抑制剂)直接传递到肿瘤细胞，提高拓扑异构酶I抑制剂的有效性和降低毒性。作为一种抗原非依赖性疗法，CBX-12药物可能对不适合抗原靶向治疗的患者具有广泛的实用性，并有潜力与其他抗癌药物和免疫疗法联合使用。 231009 pj D0317 新增作用机制内容 SXZ
Sudocetaxel Zendusortide Theratechnologies 实体瘤 TH1902 is a first-in-class PDC targeting SORT1, that consists of 2 molecules of docetaxel attached to the TH19P01 peptide via a cleavable succinyl linker. Sudocetaxel Zendusortide (TH1902) 是一种新型的sortilin受体（SORT1）靶向肽-药物共轭物（PDC），由 2 个分子的多西他赛通过可裂解的琥珀酰连接子连接到 TH19P01 肽上。 TH1902是一种具有多西紫杉醇有效载荷的PDC，它获得了FDA的快速通道指定，用于治疗对标准治疗无效的sortilin阳性复发性晚期实体瘤患者。TH1902目前正在一期临床试验中进行研究，TH1904含有阿霉素有效载荷，目前正在进行临床前研究。 231008 pj D0318 新增作用机制内容 SXZ
RP12146 Rhizen 实体瘤 An orally bioavailable, small molecule inhibitor of the nuclear enzymes poly (ADP-ribose) polymerase (PARP) 1 and 2, with potential antineoplastic activity. Upon oral administration, PARP 1/2 inhibitor RP12146 selectively binds to and inhibits PARP-1 and -2, thereby preventing PARP-1 and -2-mediated DNA repair. This promotes genetic instability and enhances the accumulation of single and double strand DNA breaks, ultimately leading to apoptosis. The PARP family of proteins catalyzes post-translational ADP-ribosylation of nuclear proteins and is activated by single-strand DNA (ssDNA) breaks. RP12146 是一种口服生物活性小分子聚（ADP-核糖）聚合酶（PARP）1 和 2 抑制剂，具有潜在的抗肿瘤活性。口服后，PARP 1/2抑制剂RP12146会选择性地与PARP-1和-2结合并抑制它们，从而阻止PARP-1和-2介导的DNA修复。这将促进遗传不稳定性，增加单链和双链 DNA 断裂的积累，最终导致细胞凋亡。PARP 蛋白家族催化核蛋白的翻译后 ADP 核糖基化，并被单链 DNA（ssDNA）断裂激活。 RP12146是新一代PARP1/2抑制剂，旨在克服与第一代PARP抑制剂相关的安全责任问题。该抑制剂的I/Ib期试验的剂量递增试验已经成功完结，正在以二期推荐剂量(RP2D)进行扩展阶段的招募。剂量相关的RP12146暴露显示出强大的靶点结合作用，并且明显没有血液学毒性（即贫血和细胞减少）。目前该研究正针对具有HRR基因突变的卵巢癌、乳腺癌和前列腺癌患者进行400mg BID剂量的扩展阶段试验。 231009 pj D0320 新增作用机制内容 SXZ
ABM-1310 璧辰医药 实体瘤 ABM-1310 is a novel small-molecule BRAF inhibitor with high water solubility, cell permeability, and blood-brain barrier penetration as demonstrated in preclinical studies. ABM-1310是一种口服的，具有高选择性、高水溶性、以及高血脑屏障渗透性的小分子BRAF抑制剂。 ABM-1310是ABM自主研发的第一个候选药物，是一种高水溶性、高细胞渗透性, 以及高血脑屏障渗透性的新一代BRAF V600X 抑制剂，具有理想的血脑屏障渗透率。在动物实验中，显著延长了中位生存期，有望成为各种恶性肿瘤脑转移的新一代BRAF抑制剂。该候选药物于2019年11月获得FDA临床试验许可，目前已经在美国进行临床I期试验。美国临床试验登记号为：NCT04190628。 230928 pj D0321 新增作用机制内容 SXZ
Pimicotinib 和誉医药 实体瘤、腱鞘巨细胞瘤 An orally bioavailable inhibitor of colony stimulating factor 1 receptor (CSF1R; CSF-1R; CD115; M-CSFR), with potential immunomodulatory and antineoplastic activities. Upon oral administration, pimicotinib targets and binds to CSF1R, thereby blocking CSF1R activation and CSF1R-mediated signaling. This inhibits the activities of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), and prevents immune suppression in the tumor microenvironment (TME). This enhances antitumor T-cell immune responses and inhibits the proliferation of tumor cells. CSF1R, also known as macrophage colony-stimulating factor receptor (M-CSFR) and CD115 (cluster of differentiation 115), is a cell-surface receptor that plays major roles in tumor cell proliferation and metastasis. Pimicotinib (ABSK021) 是一种可口服的集落刺激因子 1 受体（CSF1R；CSF-1R；CD115；M-CSFR）抑制剂，具有潜在的免疫调节和抗肿瘤活性。口服后，Pimicotinib 会靶向结合 CSF1R，从而阻断 CSF1R 的激活和 CSF1R 介导的信号传导。这将抑制肿瘤相关巨噬细胞（TAMs）和髓系来源的抑制细胞（MDSCs）的活性，并防止肿瘤微环境（TME）中的免疫抑制。这能增强抗肿瘤 T 细胞免疫反应，抑制肿瘤细胞的增殖。CSF1R又称巨噬细胞集落刺激因子受体（M-CSFR）和CD115（分化簇115），是一种细胞表面受体，在肿瘤细胞增殖和转移中发挥着重要作用。 Pimicotinib（ABSK021）是和誉医药独立自主研发的一款全新的口服、高选择性、高活性巨噬细胞集落刺激因子1受体（CSF-1R）小分子抑制剂，是中国第一个自主研发并进入全球临床III期的高选择性CSF-1R抑制剂；该药物曾获得中美两国突破性治疗药物认定，用于治疗不可手术的腱鞘巨细胞瘤。 231008 pj D0322 新增作用机制内容 SXZ
RC88 荣昌生物 实体瘤 An antibody-drug conjugate (ADC) composed of an antibody directed against the human cell surface glycoprotein mesothelin and conjugated, via a cleavable linker, to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, the antibody moiety of anti-mesothelin/MMAE ADC RC88 targets and binds to the tumor associated antigen (TAA) mesothelin on the surface of tumor cells. Upon internalization and the release of MMAE, MMAE targets and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in mesothelin-expressing tumor cells. Mesothelin is overexpressed by all mesotheliomas and a variety of other cancers, while it is minimally expressed in normal tissue. RC88 是一种抗体-药物共轭物（ADC），由针对人体细胞表面糖蛋白间皮素的抗体和通过可裂解连接体与具有潜在抗肿瘤活性的微管干扰细胞毒剂甲基澳瑞他汀 E（MMAE）共轭组成。给药后，抗间皮素/MMAE ADC RC88 的抗体分子会靶向肿瘤细胞表面的肿瘤相关抗原（TAA）间皮素并与之结合。内化和释放 MMAE 后，MMAE 靶向并与微管蛋白结合，抑制微管聚合。这导致表达间皮素的肿瘤细胞出现 G2/M 期细胞周期停滞和细胞凋亡。间皮素在所有间皮瘤和其他多种癌症中都表达过高，而在正常组织中则表达极低。 RC88是荣昌生物自主研发的靶向MSLN的ADC药物，2018年11月获批在中国开展1期临床试验，目前该试验正在进行中，初步结果显示RC88单药对MSLN表达的实体瘤具有抗肿瘤活性，安全性可控。临床前研究结果显示RC88与肿瘤细胞表面MSLN结合后，内吞进入细胞内，经蛋白酶切割释放小分子后发挥杀伤作用，使肿瘤细胞阻滞于G2/M期，从而诱导肿瘤细胞凋亡。RC88与PD-1/PD-L1等免疫检查点抑制剂（ICIs）类药物联用能诱导免疫原性细胞死亡（immunogenic cell death，ICD）的发生，释放一系列信号分子进一步激活T细胞，增强肿瘤免疫反应，协同产生更强的抗肿瘤作用。 231009 pj D0323 新增作用机制内容 SXZ
RC108 荣昌生物 实体瘤 An antibody-drug conjugate (ADC) consisting of an anti-c-Met monoclonal antibody that is conjugated to monomethyl auristatin E (MMAE), an auristatin derivative and potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration of anti-c-Met/MMAE ADC RC108, the monoclonal antibody moiety targets and binds to the c-Met protein, which is overexpressed in certain tumor types. After internalization of the agent, the MMAE moiety is released and binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and apoptosis. This inhibits the proliferation of c-Met-expressing tumor cells. c-Met, also known as hepatocyte growth factor receptor (HGFR), is a receptor tyrosine kinase that is overexpressed or mutated in many tumor cell types and plays a key role in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis. Its expression is associated with poor prognosis in many solid tumor types. RC108 是一种抗体药物共轭物（ADC），由抗-Met 单克隆抗体与甲基澳瑞他汀 E（MMAE）（一种金丝桃素衍生物和强效微管干扰剂）共轭组成，具有潜在的抗肿瘤活性。服用抗-Met/MMAE ADC RC108 后，单克隆抗体分子会靶向并结合某些肿瘤类型中过度表达的 c-Met 蛋白。药剂内化后，MMAE 分子释放出来，与微管蛋白结合并抑制其聚合，从而导致 G2/M 期停滞和细胞凋亡。c-Met 又称肝细胞生长因子受体（HGFR），是一种受体酪氨酸激酶，在许多肿瘤细胞类型中过度表达或突变，在肿瘤细胞增殖、存活、侵袭、转移和肿瘤血管生成中起关键作用。它的表达与许多实体瘤类型的不良预后有关。 RC108是荣昌生物自主研发的靶向c-MET的ADC药物，于2020年11月获批在中国开展针对c-Met阳性晚期实体瘤的1期临床试验，目前该试验正在顺利推进，初步结果显示RC108单药对c-MET表达的实体瘤具有抗肿瘤活性，安全性可控。临床前研究结果显示RC108诱导肿瘤特异性适应性免疫，增加T细胞对肿瘤微环境的浸润，而PD-1单抗则活化T细胞，增强抗肿瘤免疫反应。因此，预期RC108与信迪利单抗联用既能增强树突状细胞对肿瘤抗原的递呈，也能强化T细胞对肿瘤细胞的杀伤，从而产生增强的协同抑瘤效果。 231009 pj D0324 新增作用机制内容 SXZ
AZD9592 阿斯利康 实体瘤 An antibody-drug conjugate (ADC) composed of a bispecific antibody targeting both epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR; c-Met) and conjugated to a topoisomerase-1 inhibitor (TOP1i), with potential antineoplastic activity. Upon administration, anti-EGFR/c-Met/TOP1i ADC AZD9592 simultaneously targets and binds to the extracellular domains of wild-type (WT) or certain mutant forms of both EGFR and c-Met expressed on cancer cells. Upon binding and internalization, the TOP1i moiety is released, binds to TOP1 and stabilizes cleaved DNA-TOP1 complexes. This prevents DNA re-ligation, induces irreversible DNA strand breaks, prevents DNA repair, and leads to cycle arrest and apoptosis specifically in tumor cells expressing EGFR and c-Met. EGFR and c-Met, both upregulated or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation. AZD9592 是一种抗体药物共轭物（ADC），由靶向表皮生长因子受体（EGFR）和肝细胞生长因子受体（HGFR；c-Met）的双特异性抗体和拓扑异构酶-1抑制剂（TOP1i）组成，具有潜在的抗肿瘤活性。给药后，抗 EGFR/c-Met/TOP1i ADC AZD9592 可同时靶向并结合癌细胞上表达的野生型（WT）或某些突变型 EGFR 和 c-Met 的胞外结构域。结合和内化后，TOP1i 分子会释放出来，与 TOP1 结合并稳定已裂解的 DNA-TOP1 复合物。这可以防止 DNA 重新连接，诱导不可逆的 DNA 链断裂，阻止 DNA 修复，并导致表达表皮生长因子受体（EGFR）和 c-Met 的肿瘤细胞周期停止和凋亡。表皮生长因子受体（EGFR）和 c-Met 在多种肿瘤细胞类型中上调或突变，在肿瘤细胞增殖中发挥关键作用。 AZD9592为阿斯利康基于自有ADC平台开发的一款EGFR/c-Met双靶点ADC药物 ，而非外部合作，采用新型拓扑异构酶1载荷，旨在解决奥希替尼耐药问题。AZD9592于2022年12月22日首次启动了一项国际多中心 I 期临床试验（登记号：NCT05647122），旨在评估在AZD9592在晚期实体瘤患者中作为单一疗法或与奥希替尼联用的有效性及安全性。当前试验正在开展中，预计于2024年10月完成试验的主要指标。 231009 pj D0326 新增作用机制内容 SXZ
PRO1184 普方生物 实体瘤 An antibody-drug conjugate (ADC) composed of a human monoclonal antibody targeting folate receptor alpha (FRa; FolRa; FOLR1) conjugated, via a cleavable hydrophilic linker, to the camptothecin analog and topoisomerase 1 inhibitor exatecan, with potential antineoplastic activity. Upon administration of anti-FRalpha/exatecan ADC PRO1184, the antibody moiety targets and binds to FRa expressed on tumor cells. Upon binding, cellular uptake and linker cleavage, exatecan is released. Exatecan inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and generating DNA single- and double-strand breaks, and leading to cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of FRa-expressing tumor cells. FRa is a glycosylphosphatidylinositol linked cell-surface glycoprotein that is widely expressed in certain cancers while its expression is limited in normal tissues. PRO1184 是一种抗体药物共轭物（ADC），由靶向叶酸受体α（FRa；FolRa；FOLR1）的人类单克隆抗体与喜树碱类似物和拓扑异构酶 1 抑制剂依喜替康通过可裂解亲水连接体共轭而成，具有潜在的抗肿瘤活性。服用抗 FRα/依喜替康 ADC PRO1184 后，抗体分子会与肿瘤细胞上表达的 FRα 靶向结合。在结合、细胞摄取和连接体裂解过程中，依喜替康会被释放出来。依喜替康能抑制 DNA 拓扑异构酶 I 的活性，从而抑制 DNA 复制，产生 DNA 单链和双链断裂，导致细胞周期停滞和肿瘤细胞凋亡。这就抑制了表达 FRα 的肿瘤细胞的增殖。FRα 是一种与糖基磷脂酰肌醇相连的细胞表面糖蛋白，在某些癌症中广泛表达，而在正常组织中表达有限。 PRO1184是由叶酸受体α（FRα）抗体，与ProfoundBio专有的新型亲水接头偶联到exatecan有效载荷形成的ADC。这项首次人体研究正在美国多个临床试验中心积极招募，评估PRO1184在卵巢癌、子宫内膜癌、乳腺癌、非小细胞肺癌和间皮瘤患者中的安全性、活性和药代动力学。 231009 pj D0327 新增作用机制内容 SXZ
IAH0968 盛禾生物 结直肠癌、实体瘤 IAH0968 is an afucosylated anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody which possessing the same binding properties to HER2 as trastuzumab and improving antibody-dependent cellular cytotoxicity (ADCC) activity and superior anti-tumor efficacy. IAH0968 是一种无岩藻糖修饰（afucosylated）抗表皮生长因子受体2（HER2）单克隆抗体，与曲妥珠单抗一样具有与 HER2 结合的特性，能提高抗体依赖性细胞毒性（ADCC）活性和卓越的抗肿瘤疗效。 IAH0968是盛禾(中国)生物制药公司通过ADCC增强抗体平台（ADCC Enhanced Antibody Platform, AEA）孵化的完全岩藻糖基化敲除的抗HER2抗体，其与Fc受体的亲和力提高了20倍以上，极大地提高了对于肿瘤细胞的杀伤能力。目前，IAH0968用于标准治疗失败的HER2阳性实体瘤的Ⅰ期临床研究临近结束，对于多种晚期实体瘤末线患者，IAH0968单药治疗展现出了令人鼓舞的表现。 231009 pj D0329 新增作用机制内容 SXZ
KC1036 康辰药业 实体瘤 An orally bioavailable inhibitor of three receptor tyrosine kinases: AXL (UFO), FMS-like tyrosine kinase-3 (Flt3; CD135; fetal liver kinase-2; Flk2), and the vascular endothelial growth factor receptor type 2 (VEGFR2), with potential anti-angiogenesis and antineoplastic activities. Upon oral administration, KC1036 targets, binds to and prevents the activation of AXL, FLT3 and VEGFR2. This blocks AXL, FLT3 and VEGFR2-mediated signal transduction pathways, and inhibits both AXL-, FLT3- and VEGFR2-mediated proliferation of tumor cells and the VEGFR2-mediated proliferation, survival and migration of endothelial cells. AXL, a member of the Tyro3, AXL and Mer (TAM) family of receptor tyrosine kinases, is overexpressed by many tumor cell types and also expressed in a variety of immune cells including macrophages, natural killer (NK) cells, and regulatory T-cells (Tregs). It plays a key role in tumor cell proliferation, survival, invasion and metastasis, and is a mediator of immunosuppression. Its expression is associated with drug resistance and poor prognosis. FLT3, a class III tyrosine kinase receptor, is overexpressed or mutated in most B lineage and acute myeloid leukemias. VEGFR2 is frequently overexpressed by a variety of tumor types and tumor-associated endothelial cells. KC1036 是一种口服生物活性抑制剂，可用于抑制三种受体酪氨酸激酶：AXL（UFO）、FMS 样酪氨酸激酶-3（Flt3；CD135；胎肝激酶-2；Flk2）和血管内皮生长因子受体 2 型（VEGFR2），具有潜在的抗血管生成和抗肿瘤活性。口服 KC1036 可靶向、结合并阻止 AXL、FLT3 和 VEGFR2 的活化。这将阻断 AXL、FLT3 和 VEGFR2 介导的信号转导途径，抑制 AXL、FLT3 和 VEGFR2 介导的肿瘤细胞增殖以及 VEGFR2 介导的内皮细胞增殖、存活和迁移。AXL是受体酪氨酸激酶Tyro3、AXL和Mer（TAM）家族的成员，被许多肿瘤细胞类型过度表达，也在多种免疫细胞中表达，包括巨噬细胞、自然杀伤（NK）细胞和调节性T细胞（Tregs）。它在肿瘤细胞增殖、存活、侵袭和转移中起着关键作用，是免疫抑制的介质。它的表达与耐药性和不良预后有关。FLT3是第三类酪氨酸激酶受体，在大多数B系白血病和急性髓性白血病中过度表达或发生突变。VEGFR2 常常在多种肿瘤类型和肿瘤相关内皮细胞中过表达。 KC1036是北京康辰药业自主研发的境内外均未上市的化学药品1类创新药，于2020年1月获得国家药品监督管理局核准签发的KC1036的《临床试验通知书》（受理号：CXHL1900361、CXHL1900362）。KC1036 I期临床试验是首次人体剂量递增临床试验，评价KC1036在晚期实体肿瘤患者中的安全性和耐受性、药代动力学特性及有效性。在已入组的晚期实体瘤患者中，KC1036单药表现出良好的安全性和耐受性，并在消化系统肿瘤患者中显示出较突出的抗肿瘤活性。KC1036 Ib/II期临床试验是针对消化系统肿瘤适应症开展的更大样本量临床试验，以进一步评价KC1036治疗晚期复发或转移性消化系统肿瘤的有效性和安全性。 231009 pj D0330 新增作用机制内容 SXZ
CBP-1018 同宜医药 实体瘤 A bispecific ligand-drug conjugate targeting two as of yet undisclosed receptors and conjugated to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon administration of bispecific ligand-drug conjugate CBP-1018, the bispecific ligand moiety targets and binds to one or both of the two as of yet undisclosed receptors expressed in certain tumor types. After internalization of the agent, the cytotoxic moiety is released and kills the cancer cells expressing the receptor(s), through an as of yet unknown mechanism of action. CBP-1018 是一种双特异性配体-药物共轭物，靶向两种尚未公开的受体，并与一种尚未公开的细胞毒剂共轭，具有潜在的抗肿瘤活性。服用双特异性配体-药物共轭物 CBP-1018 后，双特异性配体分子会靶向并结合某些肿瘤类型中表达的两种尚未公开的受体中的一种或两种。药剂内化后，细胞毒性分子释放出来，通过一种尚未知晓的作用机制杀死表达受体的癌细胞。 CBP-1018是基于同宜医药Bi-XDC技术平台开发的第一款以PSMA和FRα为靶点的双配体偶联药物，同时也是全球首个自主研发的PSMA靶点偶联类新药。CBP-1018在临床前的研究数据中表现出对前列腺癌、肾细胞癌、肺腺癌和鳞癌等多种实体瘤良好的抗肿瘤效果。CBP-1018具有靶点特异性更强、在人血浆中更加稳定，水溶性更好，更容易清除等优点。 231009 pj D0331 新增作用机制内容 SXZ
NXP900 Nuvectis 实体瘤 An orally bioavailable inhibitor of SRC family of kinases (SFK), including SRC and YES1, with potential antineoplastic activity. Upon oral administration, SRC/YES1 kinase inhibitor NXP900 targets, binds to, and locks SRC and YES1 into their native closed conformation, thereby inhibiting both their kinase activity and their association with protein signaling partners. This inhibits the oncogenic signaling pathways mediated by these kinases and the proliferation of tumor cells overexpressing these kinases. SRC family of kinases are upregulated in many tumor cells and play important roles in tumor cell proliferation and metastasis. NXP900 是一种可口服的 SRC 激酶家族（SFK）（包括 SRC 和 YES1）抑制剂，具有潜在的抗肿瘤活性。口服给药后，SRC/YES1 激酶抑制剂 NXP900 会靶向、结合并锁定 SRC 和 YES1，使其进入原生封闭构象，从而抑制它们的激酶活性及其与蛋白信号伴侣的结合。这就抑制了由这些激酶介导的致癌信号通路以及过量表达这些激酶的肿瘤细胞的增殖。SRC家族激酶在许多肿瘤细胞中上调，并在肿瘤细胞增殖和转移中发挥重要作用。 Nuvectis从苏格兰爱丁堡大学获得了NXP900的全球独家权利，这是一种针对YES1和SRC的新型SRC家族激酶（SFKs）抑制剂，具有低纳摩尔效力。SFKs的过度激活在肿瘤组织中经常发生，它们是多种致癌信号传导途径的核心媒介。YES1是SFKs的一个关键成员，它增强了YAP1的磷酸化、核定位和致癌活性，YAP1是Hippo途径的一个关键效应物。在临床前研究中，NXP900在几个体内异种移植模型中表现出强大的单药抗肿瘤活性，包括在鳞状细胞癌，如宫颈癌、头颈癌和食道癌中，其中Hippo通路突变和拷贝数异常是普遍存在的。此外，NXP900在体外与奥希替尼以及在体内与恩杂鲁胺联合使用，分别证明了逆转非小细胞肺癌和转移性耐阉割前列腺癌对这些药物的获得性抗性的潜在能力。 231009 pj D0333 新增作用机制内容 SXZ
nab-sirolimus 西罗莫司(白蛋白结合型) Fyarro Aadi Bioscience 44522 FDA FYARRO is an mTOR inhibitor indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa). FYARRO是一种mTOR抑制剂，适用于治疗局部晚期不可切除或转移的恶性血管周围上皮细胞瘤（PEComa）的成年患者。 血管周围上皮细胞瘤 Sirolimus in FYARRO is an inhibitor of mechanistic target of rapamycin kinase (mTOR, previously known as mammalian target of rapamycin). mTOR, a serine threonine kinase, is downstream of the PI3K/AKT pathway, controls key cellular processes such as cell survival, growth, and proliferation, and is commonly dysregulated in several human cancers. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus-FKBP-12 complex binds to and inhibits activation of the mechanistic target of rapamycin complex 1 (mTORC1). Inhibition of mTOR by sirolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and in vivo studies. In a nonclinical study in athymic mice bearing human tumor xenografts, intravenous administration of FYARRO resulted in higher tumor accumulation of sirolimus, inhibition of an mTOR target in the tumor, and tumor growth inhibition compared to administration of an oral formulation of sirolimus at the same weekly total dose. FYARRO中的西罗莫司（Sirolimus）是一种雷帕霉素激酶（mTOR，以前称为哺乳动物雷帕霉素靶）的抑制剂。mTOR是一种丝氨酸苏氨酸激酶，是PI3K/AKT途径的下游，控制着细胞生存、生长和增殖等关键细胞过程，在几种人类癌症中普遍失调。在细胞中，西罗莫司与免疫蛋白FK结合蛋白-12（FKBP-12）结合，产生一个免疫抑制复合物。西罗莫司-FKBP-12复合物与雷帕霉素复合物1（mTORC1）的机械性靶点结合并抑制其激活。在体外和体内研究中，西罗莫司对mTOR的抑制已被证明能减少细胞增殖、血管生成和葡萄糖摄取。在一项非临床研究中，与每周总剂量相同的西罗莫司口服制剂相比，在无胸腺小鼠体内静脉注射FYARRO可使西罗莫司的肿瘤蓄积量增加，抑制肿瘤中的mTOR靶点，并抑制肿瘤的生长。 11/2021 230710 pj D0336 药物新增 SXZ
D3S-001 德昇济医药 实体瘤 An orally bioavailable inhibitor of the oncogenic KRAS substitution mutation G12C, with potential antineoplastic activity. Upon oral administration, KRAS G12C inhibitor D3S-001 selectively targets the KRAS G12C mutant and inhibits KRAS G12C-mediated signaling. This may halt proliferation and metastasis in susceptible tumor cells. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell proliferation, invasion, and metastasis. D3S-001 是一种具有潜在抗肿瘤活性的口服致癌 KRAS G12C 突变抑制剂。口服后，D3S-001 可选择性地靶向 KRAS G12C 突变，抑制 KRAS G12C 介导的信号传导。这可能会阻止易感肿瘤细胞的增殖和转移。KRAS 是 RAS 致癌基因家族的成员，在细胞信号传导、分裂和分化中发挥着重要作用。KRAS 基因突变可诱导组成性信号转导，导致肿瘤细胞增殖、侵袭和转移。 D3S-001是德昇济医药研发的首款在研新药。它是一款高活性、高选择性、差异化的KRAS G12C抑制剂，具有成药性高、对靶点的抑制性强、抑制速度快、抑制完全以及安全性好等潜在优势。目前D3S-001已获得5个国家的IND批准，并在国际多中心1期临床研究中取得积极进展。D3S-001已被FDA授予治疗KRAS G12C突变结直肠癌的快速通道资格，以及治疗KRAS G12C突变胰腺癌的孤儿药资格。 231009 pj D0339 新增作用机制内容 SXZ
D3S-002 德昇济医药 非小细胞肺癌、结直肠癌 An orally bioavailable inhibitor of the extracellular signal-regulated kinases 1 (ERK1) and 2 (ERK2), with potential antineoplastic activity. Upon oral administration, ERK1/2 inhibitor D3S-002 specifically binds to and inhibits the serine/threonine-protein kinase activities of both ERK1 and ERK2, thereby preventing the phosphorylation of ERK1/2 substrates and the activation of mitogen-activated protein kinase (MAPK)/ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent proliferation and survival of tumor cells. The MAPK/ERK pathway, also known as the RAS/RAF/MEK/ERK pathway, is hyperactivated in a variety of tumor cell types due to mutations in upstream targets. It plays a key role in the proliferation, differentiation and survival of tumor cells. D3S-002 是一种可口服的细胞外信号调节激酶 1（ERK1）和 2（ERK2）抑制剂，具有潜在的抗肿瘤活性。口服后，ERK1/2 抑制剂 D3S-002 可特异性结合并抑制 ERK1 和 ERK2 的丝氨酸/苏氨酸蛋白激酶活性，从而阻止 ERK1/2 底物的磷酸化以及有丝分裂原激活蛋白激酶 (MAPK)/ERK 介导的信号转导途径的激活。这就抑制了 ERK 依赖的肿瘤细胞增殖和存活。MAPK/ERK 通路又称 RAS/RAF/MEK/ERK 通路，在多种肿瘤细胞类型中因上游靶点突变而过度激活。它在肿瘤细胞的增殖、分化和存活过程中起着关键作用。 D3S-002片为德昇济医药肿瘤研发管线中的一款ERK1/2小分子选择性抑制剂，本次获批临床的适应症为携带MAPK通路突变的晚期实体瘤。ERK1/2处于MAPK通路最下游，在含有KRAS或BRAF突变肿瘤中发挥重要的执行以及负反馈调节作用。此外，临床前研究表明，D3S-002与KRAS G12C小分子抑制剂D3S-001联用可增强在肺癌和结肠癌中的药效及持续时间，并有潜力克服经KRAS G12C抑制剂治疗后产生的继发突变，包括KRAS二次突变、KRAS基因扩增等引起的耐药。 231009 pj D0340 新增作用机制内容 SXZ
Pimurutamab 匹姆瑞妥单抗 复宏汉霖 实体瘤、皮肤鳞状细胞癌、结直肠癌、头颈癌、肝细胞癌、肺癌 A glycoengineered humanized version of the monoclonal antibody of cetuximab, with potential antineoplastic activity. Upon intravenous administration, pimurutamab selectively targets and binds to the extracellular domain of the epidermal growth factor receptor (EGFR), thereby preventing the activation and subsequent dimerization of the receptor. This may prevent EGFR-mediated signaling and inhibit EGFR-dependent tumor cell proliferation. In addition, the glyco-optimization promotes antibody-dependent cell-mediated cytotoxicity (ADCC). EGFR, a member of the epidermal growth factor family of extracellular protein ligands, may be overexpressed on the cell surfaces of certain tumor types. Pimurutamab (HLX07) 是西妥昔单抗的糖工程人源化单克隆抗体，具有潜在的抗肿瘤活性。静脉注射后，pimurutamab 可选择性地靶向表皮生长因子受体（EGFR）的细胞外结构域并与之结合，从而阻止受体的活化和随后的二聚化。这可能会阻止表皮生长因子受体介导的信号传导，抑制依赖表皮生长因子受体的肿瘤细胞增殖。此外，糖优化还能促进抗体依赖性细胞介导的细胞毒性（ADCC）。表皮生长因子受体是表皮生长因子家族细胞外蛋白配体的成员，可能在某些肿瘤类型的细胞表面过度表达。 HLX07是复宏汉霖自主研发的针对EGFR靶点的创新型生物药，利用抗体改造平台，在西妥昔单抗的基础上，通过将HLX07的Fab区人源化，同时使该产品聚糖含量降至最低，以具备更低的免疫原性和良好的靶点亲和力。HLX07联合斯鲁利单抗用于复发或转移性头颈部鳞状细胞癌（HNSCC）、EGFR高表达鳞状非小细胞肺癌（sqNSCLC）等多种实体瘤治疗的II期临床研究已于中国完成首例患者给药；HLX07联合斯鲁利单抗贝伐珠单抗一线治疗晚期肝细胞癌（HCC）的Ⅱ期临床试验申请已获国家药品监督管理局（NMPA）批准。 231008 pj D0343 新增作用机制内容，新增中文名称 SXZ
NMS-01940153E Nerviano Medical Sciences 肝细胞癌 A selective inhibitor of the serine/threonine-protein kinase monopolar spindle 1 (Mps1; TTK), with potential antineoplastic activity. Upon administration, MPS1 kinase inhibitor NMS-01940153E targets, binds to and inhibits the activity of Mps1, a core component of the spindle assembly checkpoint (SAC). Inhibition of Mps1 activity compromises the functioning of SAC, increases chromosome missegregation errors and decreases cancer cell viability. This inhibits tumor cell proliferation. Mps1, a dual-specificity protein kinase expressed in proliferating normal tissues and aberrantly overexpressed in certain tumor types, is activated during mitosis and is essential in proper SAC function, chromosomal alignment and segregation during cellular division. NMS-01940153E 是一种丝氨酸/苏氨酸蛋白激酶单极纺锤体 1（Mps1；TTK）的选择性抑制剂，具有潜在的抗肿瘤活性。给药后，MPS1 激酶抑制剂 NMS-01940153E 靶向、结合并抑制 Mps1 的活性，Mps1 是纺锤体组装检查点（SAC）的核心成分。抑制 Mps1 的活性会损害 SAC 的功能，增加染色体错分离错误，降低癌细胞活力。这就抑制了肿瘤细胞的增殖。Mps1 是一种双特异性蛋白激酶，在增殖的正常组织中表达，在某些肿瘤类型中异常过表达，它在有丝分裂过程中被激活，对细胞分裂过程中正常的 SAC 功能、染色体排列和分离至关重要。 根据一项1/2期临床试验(MPSA-153-001)的1期结果，一种新型MPS1抑制剂，NMS-01940153E (S81694)，在复发或难治性不可切除肝细胞癌(HCC)患者中显示出临床活性。该数据在2022年EORTC-NCI-AACR分子靶点和癌症治疗研讨会上发表。 231009 pj D0345 新增作用机制内容 SXZ
Navitoclax 艾伯维 Navitoclax is an orally bioavailable small molecule inhibitor of Bcl-2 family proteins. Navitoclax targets the Bcl-2 family of proteins, the major negative regulators of apoptosis. The Bcl-2 proteins, including Bcl-2, Bcl-xL, and Bcl-w, work by binding to two other groups of proteins-the executioners (Bax, Bak) that actually start the destruction pathway, and the sentinel proteins. Cancer cells frequently overexpress the Bcl-2-like proteins, and thus, when they sustain DNA damage-from radiation, for example-they continue growing. Preventing the Bcl-2-like proteins from binding to the executioners might be able to trigger cell death in the tumor. Navitoclax是一种可口服的Bcl-2家族蛋白小分子抑制剂。Navitoclax靶向Bcl-2蛋白家族，Bcl-2蛋白家族是细胞凋亡的主要负调节因子。Bcl-2蛋白，包括Bcl-2，Bcl-xL和Bcl-w，通过与另外两组蛋白结合发挥作用--刽子手（Bax、Bak）和哨兵蛋白，前者实际上启动了凋亡途径。癌细胞经常过度表达Bcl-2样蛋白，因此，当它们受到DNA损伤（例如来自辐射的损伤）时，它们会继续生长。阻止Bcl-2样蛋白与刽子手结合可能会引发肿瘤细胞死亡。 Navitoclax已被用于研究实体瘤，非霍奇金淋巴瘤，EGFR激活突变，慢性淋巴白血病和血液恶性肿瘤等的治疗和基础科学的试验。Navitoclax是一种Bcl-2家族抑制剂。它阻断了一些阻止癌细胞死亡的酶。 231011 pj D0347 更新作用机制内容 SXZ
Mirvetuximab soravtansine-gynx 索米妥昔单抗 Elahere ImmunoGen 2022/11/14 0:00 FDA ELAHERE is a folate receptor alpha (FRα)-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. ELAHERE是一种叶酸受体α（FRα）靶向抗体和微管抑制剂结合物，适用于治疗FRα阳性、铂类耐药的上皮性卵巢癌、输卵管癌或原发性腹膜癌的成年患者，这些患者之前接受过一至三种系统性治疗方案。 卵巢癌、腹膜癌、输卵管癌 Mirvetuximab soravtansine-gynx is an antibody-drug conjugate (ADC). The antibody is a chimeric IgG1 directed against folate receptor alpha (FRα). The small molecule, DM4, is a microtubule inhibitor attached to the antibody via a cleavable linker. Upon binding to FRα, mirvetuximab soravtansine-gynx is internalized followed by intracellular release of DM4 via proteolytic cleavage. DM4 disrupts the microtubule network within the cell, resulting in cell cycle arrest and apoptotic cell death. Mirvetuximab soravtansine-gynx是一种抗体-药物结合物（ADC）。该抗体是一种针对叶酸受体α（FRα）的嵌合型IgG1。小分子DM4是一种微管抑制剂，通过一个可裂解的连接体连接到抗体上。与FRα结合后，mirvetuximab soravtansine-gynx被内化，然后通过蛋白酶裂解在细胞内释放DM4。DM4破坏了细胞内的微管网络，导致细胞周期停止和细胞凋亡。 11/2022 231103 pj D0349 新增药物中文名称 SXZ
CBP-1008 同宜医药 卵巢癌、腹膜癌、输卵管癌、实体瘤 A bispecific ligand drug conjugate targeting both human folate receptor alpha (FR alpha; FOLR1) and transient receptor potential cation channel subfamily V member 6 (TRPV6; CaT1; CATL) and conjugated to monomethyl auristatin E (MMAE), an auristatin derivative and potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration of FR alpha/TRPV6 bispecific ligand drug conjugate CBP-1008, the bispecific ligand moiety targets and binds to FR alpha and/or TRPV6, which are overexpressed in certain tumor types. After internalization of the agent, the MMAE moiety is released and binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and apoptosis. This inhibits the proliferation of tumor cells expressing FR alpha and/or TRPV6. FR alpha is a high-affinity folate-binding protein and a member of the folate receptor family; it is overexpressed in certain tumor types. The TRPV6 ion channel plays a key role in calcium homeostasis and is highly selective for calcium compared to other cations; it is overexpressed in a variety of tumors and initiates tumor cell growth, proliferation and metastases. CBP-1008 是一种双特异性配体药物共轭物，同时靶向人叶酸受体α（FRα；FOLR1）和瞬时受体电位阳离子通道 V 亚家族成员 6（TRPV6；CaT1；CATL），并与单甲基澳瑞他汀 E（MMAE）共轭，后者是一种奥瑞他汀衍生物和强效微管破坏剂，具有潜在的抗肿瘤活性。服用 FRα/TRPV6 双特异性配体药物共轭物 CBP-1008 后，双特异性配体分子会靶向并结合某些肿瘤类型中过度表达的 FRα 和/或 TRPV6。药剂内化后，MMAE 分子释放出来，与微管蛋白结合并抑制其聚合，从而导致 G2/M 期停滞和细胞凋亡。这就抑制了表达 FRα 和/或 TRPV6 的肿瘤细胞的增殖。FRα 是一种高亲和力叶酸结合蛋白，也是叶酸受体家族的成员；它在某些肿瘤类型中过度表达。TRPV6 离子通道在钙平衡中起着关键作用，与其他阳离子相比，它对钙具有高度选择性；它在多种肿瘤中过度表达，并引发肿瘤细胞的生长、增殖和转移。 同宜医药研发的CBP-1008是全球首创的双配体药物偶联药物，能同时靶向FRα和TRPV6，由优化过的特异靶向FRα/TRPV6的双配体连接子系统、可酶裂解的连接子和细胞毒素MMAE组成。2023年ASCO上公布的Ib期研究结果显示：82例铂耐药复发卵巢癌（PROC）患者接受0.15mg/kg或以上剂量的CBP-1008治疗，ORR和DCR分别为25.6%和62.2%。中位PFS为3.7个月。在34例FRα表达≥25％且既往治疗线数≤3的卵巢癌患者中，ORR为32.4％，mPFS仍为3.7个月。 231009 pj D0350 新增作用机制内容 SXZ
ARTS-021 安锐生物 实体瘤 An orally bioavailable inhibitor of cyclin-dependent kinase 2 (CDK2), with potential antineoplastic activity. Upon oral administration, CDK2 inhibitor ARTS-021 selectively targets, reversibly binds to and inhibits the activity of the CDK2/CyclinE1 (CCNE1; CCNE-1) complex. This inhibits retinoblastoma (Rb) phosphorylation and blocks G1/S transition, which leads to cell cycle arrest, the induction of apoptosis, and the inhibition of proliferation in CDK2 and/or CCNE1-overexpressing tumor cells. CDK2, a serine/threonine kinase that plays an important role in the regulation of cell cycle progression and cellular proliferation, is overexpressed in certain tumor cells. CCNE1, a regulatory factor and activator of CDK2 is overexpressed in various tumor cell types and CCNE1 overexpression elevates the activity of CDK2. ARTS-021 是一种可口服的细胞周期蛋白依赖性激酶 2（CDK2）抑制剂，具有潜在的抗肿瘤活性。口服 CDK2 抑制剂 ARTS-021 可选择性地靶向、可逆地结合 CDK2/CyclinE1（CCNE1；CCNE-1）复合物并抑制其活性。这可抑制视网膜母细胞瘤（Rb）磷酸化，阻断 G1/S 转换，从而导致细胞周期停滞，诱导细胞凋亡，并抑制 CDK2 和/或 CCNE1 表达缺失的肿瘤细胞的增殖。CDK2 是一种丝氨酸/苏氨酸激酶，在细胞周期进展和细胞增殖的调控中发挥着重要作用。CCNE1是CDK2的一种调节因子和激活因子，在多种肿瘤细胞类型中过表达，CCNE1的过表达会提高CDK2的活性。 ARTS-021是高活性高特异性的CDK2亚型选择性抑制剂，用于治疗卵巢癌、子宫内膜癌和乳腺癌等实体瘤，即将中美双报IND并且在美国首先开展临床研究 231009 pj D0354 新增作用机制内容 SXZ
MYTX-011 Mythic Therapeutics 非小细胞肺鳞癌 An antibody-drug conjugate (ADC) composed of an engineered pH-dependent humanized immunoglobulin G1 (IgG1) monoclonal antibody against the tumor-associated antigen (TAA) proto-oncogene c-Met (hepatocyte growth factor receptor; HGFR) and conjugated, via a valine-citrulline (VC) peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon intravenous administration of anti-c-Met/MMAE ADC MYTX-011, the monoclonal antibody moiety targets and binds to c-Met expressed on tumor cells. Upon binding, internalization, and proteolytic cleavage, MMAE is released. MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. This induces cell death in c-Met-expressing cancer cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis and tumor angiogenesis. The engineered pH-dependent anti-c-Met antibody allows enhanced binding and thus uptake into c-Met-expressing cancer cells while reducing binding to and uptake in healthy cells. This may increase efficacy and improve tolerability. MYTX-011 是一种抗体-药物共轭物（ADC），由一种针对肿瘤相关抗原（TAA）原癌基因 c-Met（肝细胞生长因子受体）的工程化 pH 依赖性人源化免疫球蛋白 G1（IgG1）单克隆抗体，通过缬氨酸-瓜氨酸（VC）肽链与具有潜在抗肿瘤活性的单甲基澳瑞他汀 E（MMAE）（一种金丝桃素衍生物和强效微管破坏剂）共轭而组成。静脉注射抗 Met/MMAE ADC MYTX-011 后，单克隆抗体分子会靶向并结合肿瘤细胞上表达的 c-Met。在结合、内化和蛋白水解过程中，MMAE 被释放出来。MMAE 与微管蛋白结合并抑制其聚合，导致 G2/M 期停滞和肿瘤细胞凋亡。c-Met 是一种受体酪氨酸激酶，在许多肿瘤细胞类型中过度表达或突变，在肿瘤细胞增殖、存活、侵袭、转移和肿瘤血管生成中发挥关键作用。经改造的 pH 依赖性抗-Met 抗体可增强与表达 c-Met 的癌细胞的结合，从而提高其吸收率，同时减少与健康细胞的结合和吸收。这可能会提高疗效并改善耐受性。 MYTX-011是通过Mythic创新的FateControl技术平台所开发的cMET靶向ADC，此技术可使得ADC主动导航到细胞内，从而可能增加抗癌药物对肿瘤细胞的输送，并降低对健康细胞的影响。在1期临床试验KisMET-01的首位患者给药。MYTX-011正被检视用于治疗局部晚期、复发或转移性NSCLC患者的疗效与安全性。 231009 pj D0360 新增作用机制内容 SXZ
TY-1091 同源康医药 非小细胞肺癌、甲状腺髓样癌、实体瘤 TY-1091是一款高效选择性新一代RET（转染重排）抑制剂。临床前研究结果显示，TY-1091对RET突变（RET V804L, RET V804M和RET M918T）等激酶均有较强的抑制作用，并且能够抑制获得性耐药产生的溶剂前沿突变（G810S单突变和双突变)，可潜在治疗携带激活型RET改变的多种类型肿瘤，临床上拟用于RET融合的非小细胞肺癌、RET突变型甲状腺髓样癌以及其他RET改变实体瘤的治疗。 TY-1091是由浙江同源康医药股份有限公司自主研发的一款高效选择性新一代RET（转染重排）抑制剂。临床前研究结果显示，TY-1091对RET突变（RET V804L, RET V804M和RET M918T）等激酶均有较强的抑制作用，并且能够抑制获得性耐药产生的溶剂前沿突变（G810S单突变和双突变)，可潜在治疗携带激活型RET改变的多种类型肿瘤，临床上拟用于RET融合的非小细胞肺癌、RET突变型甲状腺髓样癌以及其他RET改变实体瘤的治疗。目前正在开展一项剂量爬坡及扩展的Ⅰ/Ⅱ期临床研究。 231009 pj D0362 新增作用机制内容 SXZ
CGX1321 磷酸源生萘啶 源生医药 胃肠道肿瘤 An orally bioavailable inhibitor of the membrane-bound O-acyltransferase (MBOAT) porcupine (PORCN), with potential antineoplastic, protective and regenerative activities. Upon oral administration, PORCN inhibitor CGX1321 specifically targets and binds to PORCN in the endoplasmic reticulum (ER), thereby inhibiting the post-translational palmitoylation and secretion of Wnt ligands, thus preventing the activation of Wnt-mediated signaling, and inhibiting cell growth in Wnt-driven tumors. In addition, by inhibiting the secretion of Wnt ligands and preventing Wnt-mediated signaling, CGX1321 may also limit fibrosis and promote regeneration of certain tissues upon cell injury. PORCN catalyzes the palmitoylation of Wnt ligands, and plays a key role in Wnt ligand secretion. Wnt signaling is dysregulated in a variety of cancers and plays a key role in tumor cell proliferation. It also plays a key role in tissue regeneration. CGX1321 是一种可口服的膜结合 O-酰基转移酶（MBOAT）porcupine（PORCN）抑制剂，具有潜在的抗肿瘤、保护和再生活性。口服 PORCN 抑制剂 CGX1321 可特异性靶向并结合内质网（ER）中的 PORCN，从而抑制 Wnt 配体的翻译后棕榈酰化和分泌，从而阻止 Wnt 介导的信号激活，抑制 Wnt 驱动的肿瘤细胞生长。此外，通过抑制 Wnt 配体的分泌和阻止 Wnt 介导的信号传导，CGX1321 还可以在细胞损伤后限制纤维化并促进某些组织的再生。PORCN 催化 Wnt 配体的棕榈酰化，在 Wnt 配体分泌过程中发挥关键作用。Wnt 信号在多种癌症中失调，在肿瘤细胞增殖中起着关键作用。它在组织再生中也起着关键作用。 磷酸源生萘啶是广州源生医药科技有限公司申报的wnt通路抑制剂，用于治疗肿瘤和纤维化重大疾病。2015年7月6日，在新药创制专项的支持下按1.1类递交了临床申报，后于2016年4月获批临床。 231009 pj D0363 新增作用机制内容 SXZ
JAB-3312 加科思药业 实体瘤 JAB-3312是一种高选择性SHP2磷酸酶变构抑制剂，可以阻断RTK/RAS/MAPK信号通路，抑制RTK驱动或KRAS、BRAF Class 3、NF1功能缺失突变的肿瘤细胞的生长和增殖；同时JAB-3312可以阻断PD-1抑制信号，增强CD8+T细胞杀伤功能，并通过抑制肿瘤相关巨噬细胞功能来解除肿瘤微环境中的免疫抑制，从而发挥抗肿瘤作用。 JAB-3312和JAB-3068作为高选择性SHP2磷酸酶变构抑制剂，可以阻断RTK/RAS/MAPK信号通路，抑制RTK驱动或KRAS、BRAF Class 3、NF1功能缺失突变的肿瘤细胞的生长和增殖；同时JAB-3312和JAB-3068可以阻断PD-1抑制信号，增强CD8+T细胞杀伤功能，并通过抑制肿瘤相关巨噬细胞功能来解除肿瘤微环境中的免疫抑制，从而发挥抗肿瘤作用。现有研究表明，JAB-3312和JAB-3068可能对具有某些特定基因突变的非小细胞肺癌、头颈鳞癌、食管鳞癌、结直肠癌、胰腺癌的患者有效，以及患有第三类BRAF突变或NF1功能缺失突变实体瘤的患者或能从中获益。 231009 pj D0364 新增作用机制内容 SXZ
TAS2940 Taiho Oncology 实体瘤 An orally bioavailable, small molecule inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), with potential antineoplastic activity. Upon oral administration, EGFR/HER2 inhibitor TAS2940 targets, binds to and inhibits EGFR and HER2, which may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors. EGFR and HER2 are receptor tyrosine kinases that play major roles in tumor cell proliferation and tumor vascularization. TAS2940 是表皮生长因子受体（EGFR）和人表皮生长因子受体 2（HER2）的口服活性小分子抑制剂，具有潜在的抗肿瘤活性。口服给药后，EGFR/HER2 抑制剂 TAS2940 可靶向、结合并抑制 EGFR 和 HER2，从而抑制肿瘤生长和血管生成，并使表达 EGFR/HER2 的肿瘤消退。EGFR 和 HER2 是受体酪氨酸激酶，在肿瘤细胞增殖和肿瘤血管生成中发挥重要作用。 TAS2940是一种强效、选择性、口服生物利用度高的泛ERBB抑制剂，对多种HER2/EGFR突变和扩增的癌症具有良好的临床前疗效。此外，TAS2940在裸鼠颅内植入NCI-N87（一种HER2/EGFR突变和扩增的人胃癌细胞系）中以剂量依赖性方式抑制肿瘤生长并诱导肿瘤消退。 231009 pj D0365 新增作用机制内容 SXZ
PF-07799933 辉瑞 实体瘤 An orally bioavailable class 1 and 2 inhibitor of the serine/threonine-protein kinase B-raf (BRAF) protein, with potential antineoplastic activity. Upon oral administration, BRAF inhibitor PF-07799933 selectively binds to and inhibits the activity of class 1 and 2 BRAF alterations. This inhibits the proliferation of tumor cells which express these BRAF alterations. BRAF, a member of the raf family of serine/threonine protein kinases, plays a role in the regulation of mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways, which may be constitutively activated due to BRAF gene mutations. Mutated forms and fusions of BRAF are associated with a number of neoplastic diseases. PF-07799933 是一种可口服的丝氨酸/苏氨酸蛋白激酶 B-raf（BRAF）蛋白 1 类和 2 类抑制剂，具有潜在的抗肿瘤活性。口服后，BRAF 抑制剂 PF-07799933 可选择性地与 1 类和 2 类 BRAF 改变结合并抑制其活性。这将抑制表达这些 BRAF 改变的肿瘤细胞的增殖。BRAF 是丝氨酸/苏氨酸蛋白激酶 raf 家族的成员，在有丝分裂原激活蛋白激酶 (MAPK) 和细胞外信号调节激酶 (ERK) 信号通路的调控中发挥作用。BRAF 基因突变和融合与多种肿瘤性疾病有关。 PF-07799933是一种ATP竞争性RAF抑制剂，对BRAF突变具有活性，可抑制肿瘤生长。 231009 pj D0366 新增作用机制内容 SXZ
Necitumumab 耐昔妥珠单抗 Portrazza 礼来 42332 FDA PORTRAZZA is an epidermal growth factor receptor (EGFR) antagonist indicated, in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer. PORTRAZZA是一种表皮生长因子受体（EGFR）拮抗剂，与吉西他滨和顺铂联合用于转移性鳞状非小细胞肺癌患者的一线治疗。 鳞状非小细胞肺癌 Necitumumab is a recombinant human lgG1 monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands. Expression and activation of EGFR has been correlated with malignant progression, induction of angiogenesis, and inhibition of apoptosis. Binding of necitumumab induces EGFR internalization and degradation in vitro. In vitro, binding of necitumumab also led to antibody-dependent cellular cytotoxicity (ADCC) in EGFR-expressing cells. In in vivo studies using xenograft models of human cancer, including non-small cell lung carcinoma, administration of necitumumab to implanted mice resulted in increased antitumor activity in combination with gemcitabine and cisplatin as compared to mice receiving gemcitabine and cisplatin alone. Necitumumab是一种重组人lgG1单克隆抗体，能与人表皮生长因子受体（EGFR）结合并阻断EGFR与其配体的结合。表皮生长因子受体的表达和活化与恶性进展、诱导血管生成和抑制细胞凋亡有关。在体外，与necitumumab结合可诱导表皮生长因子受体内化和降解。在体外，与necitumumab结合还可导致表达表皮生长因子受体的细胞产生抗体依赖性细胞毒性（ADCC）。在使用人类癌症（包括非小细胞肺癌）异种移植模型的体内研究中，与单独接受吉西他滨和顺铂治疗的小鼠相比，给植入的小鼠注射necitumumab与吉西他滨和顺铂联合治疗可提高抗肿瘤活性。 11/2015 230712 pj D0368 药物新增 lxl
HS-10241 翰森制药 非小细胞肺癌、实体瘤 An orally bioavailable small molecule inhibitor of the oncoprotein c-Met (hepatocyte growth factor receptor; HGFR), with potential antineoplastic activity. Upon oral administration, HS-10241 targets and binds to the c-Met protein, prevents c-Met phosphorylation and disrupts c-Met-dependent signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis. HS-10241 是一种口服活性小分子肿瘤蛋白 c-Met（肝细胞生长因子受体；HGFR）抑制剂，具有潜在的抗肿瘤活性。口服后，HS-10241 可靶向结合 c-Met 蛋白，阻止 c-Met 磷酸化，并破坏 c-Met 依赖性信号转导途径。c-Met 蛋白在许多肿瘤细胞类型中过度表达或突变，在肿瘤细胞增殖、存活、侵袭、转移和肿瘤血管生成中发挥关键作用。 HS-10241是翰森制药开发的特异性酪氨酸激酶抑制剂。对c-MET激酶的活性抑制具有很强的特异性，选择性抑制c-MET高表达的肿瘤细胞和动物模型肿瘤；安全性良好 231009 pj D0370 新增作用机制内容 SXZ
VIC-1911 捷思英达 非小细胞肺癌、肝细胞癌 An orally bioavailable inhibitor of the serine/threonine protein kinase aurora A, with potential antimitotic and antineoplastic activities. Upon intravenous administration, aurora A kinase inhibitor VIC-1911 binds to and inhibits aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, inhibition of cell division and the induction of apoptosis in cells overexpressing aurora A kinase. Aurora A kinase localizes to the spindle poles and to spindle microtubules during mitosis; it plays an essential role in the regulation of spindle assembly. Aurora kinase A is overexpressed in a wide variety of cancers. VIC-1911 是一种可口服的丝氨酸/苏氨酸蛋白激酶 Aurora A 抑制剂，具有潜在的抗有丝分裂和抗肿瘤活性。静脉给药后，Aurora A 激酶抑制剂 VIC-1911 与 Aurora A 激酶结合并对其产生抑制作用，这可能会破坏有丝分裂纺锤体的组装，破坏染色体分离，抑制细胞分裂，并诱导过量表达 Aurora A 激酶的细胞凋亡。Aurora A 激酶在有丝分裂过程中定位在纺锤体两极和纺锤体微管上，在纺锤体组装的调节过程中发挥着重要作用。Aurora A 激酶在多种癌症中过度表达。 Aurora A激酶是一种参与细胞有丝分裂的丝氨酸/苏氨酸蛋白酶，在抑制靶向药耐药机制的形成、合成致死DNA损伤修复等领域有非常重要的临床应用。VIC-1911是捷思英达引进的一款具有“first-in-class”潜力的新一代高选择性的Aurora A激酶抑制剂。最初该药由日本Taiho Pharmaceutical公司开发（原研发代号为TAS-119），Vitrac公司现拥有该药在肿瘤领域的全球独家开发和商业化权利，其中捷思英达将独家负责VIC-1911在大中华区的开发和商业化。此前，VIC-1911已在美国已经完成了临床1期单药爬坡研究，并确定了临床2期推荐剂量（RP2D）。捷思英达子公司Vitrac Therapeutics将在近期启动针对KRAS基因突变肺癌的临床1/2期研究，及一项未披露适应症的研究者发起临床研究。 231009 pj D0371 新增作用机制内容 SXZ
GEC255 健艾仕生物 实体瘤 An orally bioavailable small molecule inhibitor of the oncogenic KRAS substitution mutation G12C, with potential antineoplastic activity. Upon oral administration, KRAS G12C inhibitor GEC255 selectively targets the KRAS G12C mutant and inhibits KRAS G12C-mediated signaling. This may halt proliferation and metastasis in susceptible tumor cells. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell proliferation, invasion, and metastasis. GEC255 是一种口服生物活性小分子抑制剂，用于抑制致癌 KRAS G12C 基因突变，具有潜在的抗肿瘤活性。口服后，KRAS G12C 抑制剂 GEC255 可选择性地靶向 KRAS G12C 突变，抑制 KRAS G12C 介导的信号传导。这可能会阻止易感肿瘤细胞的增殖和转移。KRAS 是 RAS 致癌基因家族的成员，在细胞信号传导、分裂和分化中发挥着重要作用。KRAS 基因突变可诱导组成性信号转导，导致肿瘤细胞增殖、侵袭和转移。 KRAS 突变是非小细胞肺癌（NSCLC）中最常见的致癌驱动因素之一，其中 G12C 是占比最高的 KRAS 突变。GEC255 是一种新型小分子药物，具有高选择性、优异的靶点结合能力、良好的药理学特性，在 KRAS G12C 突变晚期 NSCLC 患者中显示出有希望的抗肿瘤活性。 231009 pj D0372 新增作用机制内容 SXZ
M1231 Sutro 实体瘤 An antibody drug conjugate (ADC) composed of a bispecific antibody directed against the tumor associated antigens (TAAs) mucin-1 (MUC1) and human epidermal growth factor receptor (EGFR), conjugated, via a cleavable valine-citruline-based linker, to the hemiasterlin-related toxic warhead, with potential antineoplastic activity. Upon intravenous administration, the antibody moiety of anti-MUC1/EGFR bispecific ADC M1231 targets and binds to MUC1 and EGFR expressed on certain tumor cells. Upon binding, internalization, and enzymatic cleavage, the cytotoxic hemiasterlin moiety of M1231 binds to the vinca domain on tubulin, resulting in inhibition of tubulin polymerization and microtubule assembly, depolymerization of existing microtubules, inhibition of mitosis, and inhibition of cellular proliferation. MUC1 and EGFR, overexpressed on the surface of a variety of cancer cells, play key roles in tumor cell survival and proliferation. MUC1 and EGFR are often co-localized due to loss of membrane polarization on tumor cells while co-expression in normal cells is limited. M1231 是一种抗体药物共轭物（ADC），由针对肿瘤相关抗原（TAA）粘蛋白-1（MUC1）和人表皮生长因子受体（EGFR）的双特异性抗体组成，通过可裂解的缬氨酸-瓜氨酸连接子与 hemiasterlin 相关毒性弹头连接，具有潜在的抗肿瘤活性。静脉注射后，抗 MUC1/EGFR 双特异性 ADC M1231 的抗体分子会靶向并结合某些肿瘤细胞上表达的 MUC1 和表皮生长因子受体。在结合、内化和酶解过程中，M1231 的细胞毒性 hemiasterlin 分子会与微管蛋白上的 vinca 位点结合，从而抑制微管蛋白聚合和微管组装，使现有微管解聚，抑制有丝分裂，抑制细胞增殖。MUC1 和表皮生长因子受体（EGFR）在多种癌细胞表面过度表达，在肿瘤细胞的存活和增殖中发挥着关键作用。由于肿瘤细胞膜极化的丧失，MUC1 和表皮生长因子受体经常共定位，而在正常细胞中的共表达却很有限。 M1231是一款同时靶向MUC1-EGFR的双特异性抗体偶联物（ADC），用于治疗实体肿瘤。M1231基于Sutro公司的XpressCF和XpressCF+技术平台开发，同时依赖于德国默克的strand-exchange工程结构域（SEED）平台生产的双特异性抗样分子，此外M1231还利用了Sutro公司专有的连接子。 231009 pj D0373 新增作用机制内容 SXZ
Davutamig 再生元 实体瘤 A bispecific monoclonal antibody that targets two different epitopes of the human tumor-associated antigen (TAA) MET (c-MET; hepatocyte growth factor receptor; HGFR), with potential antineoplastic activity. Upon administration, davutamig targets and binds to two different, non-overlapping epitopes on MET expressed on thd tumor cell surface, thereby forming unique davutamig-MET complexes. The binding of davutamig to the MET epitopes and the unique complex formation causes MET internalization and degradation. This prevents MET-mediated signaling and inhibits growth of MET-driven tumor cells. MET, a receptor tyrosine kinase, is overexpressed on the cell surfaces of various solid tumor cell types where it is involved in epithelial-mesenchymal transition; it plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis. Davutamig (REGN5093) 是一种双特异性单克隆抗体，靶向人类肿瘤相关抗原（TAA）MET（c-MET；肝细胞生长因子受体；HGFR）的两个不同表位，具有潜在的抗肿瘤活性。给药后，davutamig 会靶向表达在肿瘤细胞表面的 MET 上的两个不同且不重叠的表位并与之结合，从而形成独特的 davutamig-MET 复合物。davutamig 与 MET 表位的结合以及独特复合物的形成会导致 MET 内化和降解。这就阻止了 MET 介导的信号传导，抑制了 MET 驱动的肿瘤细胞的生长。MET 是一种受体酪氨酸激酶，在各种实体瘤细胞表面过度表达，参与上皮-间质转化；在癌细胞生长、存活、血管生成、侵袭和转移中起着关键作用。 REGN5093是靶向MET受体不同位置的双特异性抗体，当REGN5093与肿瘤细胞上的MET受体结合时，会引发此抗体-受体复合物快速内化于细胞中，造成持续MET受体的降解，进而阻断其支持细胞增殖的能力。 231009 pj D0374 新增作用机制内容 SXZ
REGN5093-M114 再生元 实体瘤 An antibody-drug conjugate (ADC) consisting of REGN5093, a biparatopic monoclonal antibody that targets two different epitopes of the human tumor-associated antigen (TAA) MET (c-MET; hepatocyte growth factor receptor; HGFR), and conjugated, via a protease cleavable linker, to the cytotoxic maytansine derivative M24, with potential antineoplastic activity. Upon administration of anti-MET x MET ADC REGN5093-M114, the REGN5093 moiety targets and binds to two different, non-overlapping epitopes on MET expressed on the tumor cell surface. After antibody-antigen interaction followed by internalization and protease cleavage, the maytansine M24 moiety binds to tubulin, inhibits microtubule assembly, and induces microtubule disassembly. This leads to a disruption of mitosis and the inhibition of cell proliferation in cancer cells expressing MET. MET, a receptor tyrosine kinase, is overexpressed on the cell surfaces of various solid tumor cell types where it is involved in epithelial-mesenchymal transition; it plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis. REGN5093-M114 是一种抗体药物共轭物（ADC），由针对人类肿瘤相关抗原（TAA）MET（c-MET；肝细胞生长因子受体；HGFR）的两个不同表位的双位单克隆抗体 REGN5093 组成，并通过蛋白酶可裂解连接子与具有细胞毒性的 maytansine 衍生物 M24 共轭，具有潜在的抗肿瘤活性。服用抗 MET x MET ADC REGN5093-M114 后，REGN5093 分子会靶向并结合肿瘤细胞表面表达的 MET 上两个不同的、非重叠的表位。在抗体与抗原相互作用后，经过内化和蛋白酶裂解，maytansine M24分子与微管蛋白结合，抑制微管组装并诱导微管解体。这导致表达 MET 的癌细胞有丝分裂中断，细胞增殖受到抑制。MET 是一种受体酪氨酸激酶，在各种实体瘤细胞表面过度表达，参与上皮-间质转化；在癌细胞生长、存活、血管生成、侵袭和转移中发挥关键作用。 REGN5093-M114是由Regenron（再生元）开发的双抗ADC，该抗体为1+1非对称型双特异抗体，该抗体本身同样具有一定的抑制肿瘤的效果。该药物通过M114 linker将抗体与毒素M24（美登素衍生物）连接，可以同时结合两个MET的不同的表位，可以有效阻断HGF与MET的结合，从而抑制相关通路。此外，抗体结合肿瘤细胞表面的MET后形成的2+2型复合物可以被内化，进入肿瘤细胞并在溶酶体中被降解，减少MET通过再循环表达在细胞表面。除此之外，REGN5093-M114中可以被酶切的linker在溶酶体中被酶切后释放M24毒素并通过作用于微管蛋白来抑制肿瘤生长。目前，该药物针对非小细胞肺癌的临床试验正在进行。 231009 pj D0375 新增作用机制内容 SXZ
BLU-451 Blueprint 实体瘤 An orally bioavailable, central nervous system (CNS) penetrating, mutant-selective covalent inhibitor of epidermal growth factor receptor (EGFR) exon 20 insertion (Ex20ins) activating mutations, with potential antineoplastic activity. Upon oral administration, EGFR Ex20ins inhibitor BLU-451 selectively targets, irreversibly binds to and inhibits the activity of EGFR Ex20ins and some other oncogenic point mutations. This prevents EGFR Ex20ins-mediated signaling. This may induce cell death and inhibit tumor growth in EGFR Ex20ins-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumors, plays a key role in tumor cell proliferation and tumor vascularization. BLU-451 is able to penetrate the blood-brain-barrier (BBB) and may therefore exert its activity against EGFR Ex20ins-driven CNS primary tumors and CNS metastases. BLU-451 does not inhibit the activity of wild-type (WT) EGFR. EGFR Ex20ins are oncogenic driver mutations that constitutively upregulate kinase activity. BLU-451 是一种表皮生长因子受体（EGFR）20 外显子插入（Ex20ins）激活突变的口服生物活性、中枢神经系统（CNS）穿透性、突变选择性共价抑制剂，具有潜在的抗肿瘤活性。表皮生长因子受体 Ex20ins 抑制剂 BLU-451 口服后可选择性地靶向、不可逆地结合并抑制表皮生长因子受体 Ex20ins 和其他一些致癌点突变的活性。这就阻止了表皮生长因子受体 Ex20ins 介导的信号转导。这可能会诱导细胞死亡，并抑制表皮生长因子受体 Ex20ins 表达的肿瘤细胞的肿瘤生长。表皮生长因子受体是一种在许多肿瘤中发生突变的受体酪氨酸激酶，在肿瘤细胞增殖和肿瘤血管形成中起着关键作用。BLU-451 能够穿透血脑屏障（BBB），因此可对表皮生长因子受体 Ex20ins 驱动的中枢神经系统原发性肿瘤和中枢神经系统转移瘤发挥活性。BLU-451 不抑制野生型（WT）表皮生长因子受体的活性。表皮生长因子受体 Ex20ins 是构成性上调激酶活性的致癌驱动突变。 BLU-451是一种中枢神经系统穿透性、野生型保留、共价小分子抑制剂，可抑制表皮生长因子受体ex20ins以及非典型（G719C、G719S、L861Q）和常见的表皮生长因子受体突变体。临床前数据显示，BLU-451具有强大的抗肿瘤活性，包括在颅内异种移植模型中的活性。 231009 pj D0376 新增作用机制内容 SXZ
IMM2902 宜明昂科 实体瘤 A bispecific antibody directed against both the human tyrosine kinase receptor epidermal growth factor receptor 2 (HER2; ErbB2; HER-2) and the human cell surface antigen CD47, with potential immunostimulating, phagocytosis-inducing and antineoplastic activities. Upon administration of anti-CD47/anti-HER2 bispecific antibody IMM2902, the anti-HER2 moiety selectively targets and binds to the tumor-associated antigen (TAA) HER2 on HER2-expressing tumor cells, thereby improving the binding of the anti-CD47 moiety to the HER2-expressing tumor cells. The CD47 binding by IMM2902 blocks the interaction of CD47 with signal regulatory protein alpha (SIRPalpha), an inhibitory protein expressed on macrophages and dendritic cells (DCs), which prevents CD47/SIRPalpha-mediated signaling and abrogates the CD47/SIRPalpha-mediated inhibition of phagocytosis. This induces pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed on macrophages, which results in macrophage activation and the specific phagocytosis of the HER2-expressing tumor cells. Additionally, blocking CD47 signaling activates an anti-tumor T-lymphocyte immune response and T-cell-mediated killing of HER2-expressing tumor cells. IMM2902 may also induce an anti-tumor activity through the induction of antibody-dependent cellular cytotoxicity (ADCC). CD47, also called integrin-associated protein (IAP), is widely expressed on normal, healthy cells, such as red blood cells and platelets, and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPalpha, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate. HER-2, overexpressed on a variety of tumor cell types, plays an important role in tumor cell proliferation, differentiation and survival. Co-targeting CD47 and HER2 may limit the binding of IMM2902 to CD47 on healthy hematopoietic stem cells (HSCs) and may minimize any associated adverse effects. IMM2902 是一种同时针对人类酪氨酸激酶受体表皮生长因子受体 2（HER2；ErbB2；HER-2）和人类细胞表面抗原 CD47 的双特异性抗体，具有潜在的免疫刺激、吞噬诱导和抗肿瘤活性。服用抗 CD47/抗 HER2 双特异性抗体 IMM2902 后，抗 HER2 分子会选择性地靶向表达 HER2 的肿瘤细胞上的肿瘤相关抗原（TAA）HER2 并与之结合，从而改善抗 CD47 分子与表达 HER2 的肿瘤细胞的结合。IMM2902 与 CD47 的结合可阻断 CD47 与信号调节蛋白α（SIRPalpha）的相互作用，信号调节蛋白α是一种表达在巨噬细胞和树突状细胞（DC）上的抑制蛋白，它可阻止 CD47/SIRPalpha 介导的信号传导，并削弱 CD47/SIRPalpha 介导的吞噬抑制作用。这诱导了由肿瘤细胞表面特异表达的钙调蛋白（CRT）与巨噬细胞上表达的低密度脂蛋白（LDL）受体相关蛋白（LRP）结合所介导的促吞噬信号，从而导致巨噬细胞活化并特异性地吞噬 HER2 表达的肿瘤细胞。此外，阻断 CD47 信号传导可激活抗肿瘤 T 淋巴细胞免疫反应和 T 细胞介导的对 HER2 表达肿瘤细胞的杀伤。IMM2902 还可通过诱导抗体依赖性细胞毒性（ADCC）诱导抗肿瘤活性。CD47 又称整合素相关蛋白（IAP），在红细胞和血小板等正常健康细胞上广泛表达，在多种癌细胞表面过度表达。CD47 的表达及其与 SIRPalpha 的相互作用会抑制巨噬细胞的活化，保护癌细胞不被吞噬，从而使癌细胞得以增殖。HER-2 在多种肿瘤细胞类型中过度表达，在肿瘤细胞增殖、分化和存活过程中发挥着重要作用。共同靶向 CD47 和 HER2 可限制 IMM2902 与健康造血干细胞 (HSC) 上的 CD47 结合，并可最大限度地减少相关的不良反应。 IMM2902 是一款靶向人CD47xHer2的First-In-Class产品。一方
WSD0922-Fu 威尚生物 非小细胞肺癌、高级别星形细胞瘤 A blood-brain-barrier (BBB) penetrable selective inhibitor of epidermal growth factor receptor (EGFR) and various EGFR mutations, including but not limited to the EGFR variant III (EGFRvIII) mutant form, with potential antineoplastic activity. Upon administration of EGFR/EGFRvIII inhibitor WSD0922-FU, this agent is able to penetrate the BBB and specifically targets, binds to and inhibits EGFR and specific EGFR mutations, which prevents EGFR/EGFR mutant-mediated signaling and leads to cell death in EGFR/EGFR mutant-expressing tumor cells. Compared to other EGFR inhibitors that are not able to penetrate the BBB, WSD0922-FU may have therapeutic benefits in brain tumors, such as glioblastoma (GBM) and metastatic CNS tumors. EGFR, a receptor tyrosine kinase (RTK) that is mutated in many tumor cell types, plays a key role in tumor cell proliferation and survival. WSD0922-Fu 是一种可穿透血脑屏障（BBB）的表皮生长因子受体（EGFR）和各种 EGFR 突变的选择性抑制剂，包括但不限于 EGFR 变体 III（EGFRvIII）突变，具有潜在的抗肿瘤活性。服用 EGFR/EGFRvIII 抑制剂 WSD0922-FU 后，该药物能够穿透 BBB ，特异性地靶向、结合并抑制 EGFR 和特定的 EGFR 突变，从而阻止 EGFR/EGFR 突变介导的信号传导，导致表达 EGFR/EGFR 突变的肿瘤细胞死亡。与其他不能穿透 BBB 的 EGFR 抑制剂相比，WSD0922-FU 可能对胶质母细胞瘤（GBM）和转移性中枢神经系统肿瘤等脑肿瘤有治疗效果。表皮生长因子受体（EGFR）是一种在许多肿瘤细胞类型中发生突变的受体酪氨酸激酶（RTK），在肿瘤细胞的增殖和存活中起着关键作用。 WSD0922-Fu是一种可穿透血脑屏障（BBB）的表皮生长因子受体（EGFR）和各种EGFR突变的选择性抑制剂，包括但不限于EGFR变异体III（EGFRvIII）突变形式，具有潜在的抗肿瘤活性。服用表皮生长因子受体/表皮生长因子受体vIII抑制剂WSD0922-FU后，该制剂能够穿透BBB，特异性靶向、结合并抑制表皮生长因子受体和特定的表皮生长因子受体突变，从而阻止表皮生长因子受体/表皮生长因子受体突变介导的信号转导，导致表皮生长因子受体/表皮生长因子受体突变表达的肿瘤细胞死亡。与其他不能穿透BBB的表皮生长因子受体抑制剂相比，WSD0922-FU可能对胶质母细胞瘤（GBM）和转移性中枢神经系统肿瘤等脑肿瘤有治疗效果。表皮生长因子受体（EGFR）是一种受体酪氨酸激酶（RTK），在许多肿瘤细胞类型中发生突变，在肿瘤细胞增殖和存活中起着关键作用。 231009 pj D0379 新增作用机制内容 SXZ
FCN-159 复创医药 神经纤维瘤、低级别胶质瘤、黑色素瘤 An orally bioavailable inhibitor of mitogen-activated protein kinase kinase (MAP2K, MAPK/ERK kinase, or MEK) 1 and 2, with potential antineoplastic activity. Upon administration, MEK 1/2 Inhibitor FCN-159 selectively binds to and inhibits the activity of MEK1 and MEK2, preventing the activation of MEK1/2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK1/2 are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway that regulates cell growth. This pathway is often dysregulated in a variety of tumor cell types through BRAF, KRAS and NRAS mutations. FCN-159 是一种口服丝裂原活化蛋白激酶激酶（MAP2K、MAPK/ERK 激酶或 MEK）1 和 2 抑制剂，具有潜在的抗肿瘤活性。给药后，MEK 1/2抑制剂FCN-159会选择性地与MEK1和MEK2结合并抑制其活性，阻止依赖MEK1/2的效应蛋白和转录因子的激活，从而抑制生长因子介导的细胞信号传导和肿瘤细胞增殖。MEK1/2 是具有双重特异性的苏氨酸/酪氨酸激酶，在激活调节细胞生长的 RAS/RAF/MEK/ERK 通路中发挥着关键作用。在多种肿瘤细胞类型中，该通路往往因 BRAF、KRAS 和 NRAS 突变而失调。 FCN-159片由复星医药自主研发，是一款口服有效的小分子MEK1/2选择性抑制剂，拟主要用于晚期实体瘤、I型神经纤维瘤、组织细胞肿瘤、动静脉畸形的治疗。能显著抑制RAS/RAF突变的肿瘤细胞增殖，通过抑制MEK激酶的磷酸化达到抑制或阻断下游通路的作用，阻断细胞内ERK蛋白的磷酸化，阻滞细胞周期于G0/G1期和诱导细胞凋亡，从而实现抗肿瘤作用。与曲美替尼相比，FCN-159对活化的MEK1和MEK2的选择性高出10倍以上，并且在两种具有NRAS突变的患者来源的异种移植（PDX）模型中显示出显著的抗肿瘤生长抑制作用。2023年4月21日，CDE官网显示，复星医药1类化药FCN-159片纳入突破性疗法，用于组织细胞肿瘤患者的治疗。 231009 pj D0380 新增作用机制内容 SXZ
FS-1502 重组HER2人源化单抗单甲基奥瑞他汀F偶联剂 复星医药 非小细胞肺癌、结直肠癌、乳腺癌、胃癌、实体瘤 An antibody-drug conjugate (ADC) composed of trastuzumab, a humanized monoclonal antibody targeting the tumor-associated antigen (TAA) epidermal growth factor receptor 2 (EGFR2; HER2; ErbB2), site-specifically conjugated, via a tumor-selective beta-glucuronide linker, to the auristatin analog and potent microtubule inhibitor monomethyl auristatin F (MMAF), with potential antineoplastic activity. Upon administration of trastuzumab/MMAF ADC IKS014, the trastuzumab moiety targets and binds to HER2 expressed on tumor cells. Upon binding, internalization and linker cleavage, MMAF is released. MMAF binds to and inhibits tubulin polymerization, which results in G2/M phase arrest and tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. FS-1502 (IKS014; LCB14-0110) 是一种抗体药物共轭物（ADC），由靶向肿瘤相关抗原（TAA）表皮生长因子受体 2（EGFR2；HER2；ErbB2）的人源化单克隆抗体曲妥珠单抗组成，通过肿瘤选择性β-葡萄糖醛酸连接体与具有潜在抗肿瘤活性的金丝桃素类似物和强效微管抑制剂单甲基澳瑞他汀 F（MMAF）定点共轭。服用 FS-1502 后，曲妥珠单抗分子会与肿瘤细胞上表达的 HER2 靶向结合。结合、内化和连接体裂解后，MMAF 被释放出来。MMAF 与小管蛋白结合并抑制其聚合，从而导致 G2/M 期停滞和肿瘤细胞凋亡。HER2 是一种酪氨酸激酶受体，在许多癌细胞类型中过度表达。 FS-1502由复星医药控股子公司上海复星医药产业发展有限公司（“复星医药产业”）开发，属于新一代定点偶联裂解型抗体偶联药物，在单抗轻链末端定点偶联连接子和细胞毒素，拟用于治疗HER2阳性的晚期乳腺癌及晚期恶性肿瘤，目前进展顺利，多个瘤种在2/3期阶段推进。 231008 pj D0381 新增作用机制内容 SXZ
PRT811 Prelude Therapeutics 实体瘤 An orally available small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5), with potential antiproliferative and antineoplastic activities. Upon oral administration, PRMT5 inhibitor PRT811 selectively binds to PRMT5 and inhibits its function. By inhibiting its methyltransferase activity, levels of both monomethylated and dimethylated arginine residues in histones H2A, H3 and H4 are decreased. This modulates the expression of genes involved in several cellular processes, including cellular proliferation. This may increase the expression of antiproliferative genes and/or decrease the expression of genes that promote cell proliferation, which may lead to decreased growth of rapidly proliferating cells, including cancer cells. PRMT5, a type II methyltransferase that catalyzes the formation of both omega-N monomethylarginine (MMA) and symmetric dimethylarginine (sDMA) on histones and a variety of other protein substrates involved in signal transduction and cellular transcription, is overexpressed in several neoplasms. Elevated levels are associated with decreased patient survival. PRT811是一种可口服的小分子精氨酸蛋白甲基转移酶 5 (PRMT5) 抑制剂，具有潜在的抗增殖和抗肿瘤活性。口服后，PRMT5 抑制剂 PRT811 可选择性地与 PRMT5 结合并抑制其功能。通过抑制其甲基转移酶活性，组蛋白 H2A、H3 和 H4 中的单甲基化和二甲基化精氨酸残基水平都会降低。这会调节参与细胞增殖等多个细胞过程的基因的表达。这可能会增加抗增殖基因的表达和/或减少促进细胞增殖基因的表达，从而导致快速增殖细胞（包括癌细胞）的生长速度下降。PRMT5 是一种 II 型甲基转移酶，可催化组蛋白和其他多种参与信号转导和细胞转录的蛋白质底物上ω-N 甲基精氨酸（MMA）和对称二甲基精氨酸（sDMA）的形成。其水平升高与患者存活率下降有关。 PRT811是一种可口服的蛋白精氨酸甲基转移酶5（PRMT5）小分子抑制剂，具有潜在的抗增殖和抗肿瘤活性。口服PRMT5抑制剂PRT811可选择性地与PRMT5结合并抑制其功能。通过抑制其甲基转移酶活性，组蛋白H2A、H3和H4中单甲基化和二甲基化精氨酸残基的水平均会降低。这将调节参与多种细胞过程（包括细胞增殖）的基因的表达。这可能会增加抗增殖基因的表达和/或降低促进细胞增殖基因的表达，从而导致快速增殖细胞（包括癌细胞）的生长速度降低。PRMT5是一种II型甲基转移酶，可催化组蛋白和其他多种参与信号转导和细胞转录的蛋白质底物上ω-N一甲基精氨酸（MMA）和对称二甲基精氨酸（sDMA）的形成。其水平升高与患者生存率下降有关。 231008 pj D0385 新增作用机制内容 SXZ
BAT8009 百奥泰 实体瘤 An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) linked to the camptothecin analog exatecan, with potential antineoplastic activity. Upon administration of anti-B7-H3 ADC BAT8009, the anti-B7-H3 antibody moiety targets and binds to B7-H3-expressing tumor cells. Upon binding, internalization and linker cleavage, exatecan is released. Exatecan inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of B7-H3-expressing tumor cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It is a negative regulator of T-cell activation and its overexpression plays a key role in tumor cell invasion and metastasis. BAT8009 是一种抗体药物共轭物（ADC），由针对免疫调节蛋白 B7-同源物 3（B7-H3，CD276）的人源化单克隆抗体与喜树碱类似物依喜替康连接而成，具有潜在的抗肿瘤活性。服用抗 B7-H3 ADC BAT8009 后，抗 B7-H3 抗体分子会靶向表达 B7-H3 的肿瘤细胞并与之结合。结合、内化和连接体裂解后，依喜替康会释放出来。依喜替康可抑制 DNA 拓扑异构酶 I 的活性，从而抑制 DNA 复制，导致细胞周期停滞和肿瘤细胞凋亡。这就抑制了表达 B7-H3 的肿瘤细胞的增殖。B7-H3 是一种 I 型跨膜蛋白，属于 B7 协同刺激蛋白超家族，在某些肿瘤细胞类型和各种免疫细胞上过度表达。它是 T 细胞活化的负调控因子，其过度表达在肿瘤细胞侵袭和转移中起着关键作用。 BAT8009是百奥泰开发的B7H3靶向的ADC，由重组人源化抗B7H3抗体与毒性小分子拓扑异构酶I抑制剂，通过自主研发的可剪切连接子连接而成。在体内外药理研究中，BAT8009表现出高效的抗肿瘤活性，是一款潜在的靶向B7H3的“best-in-class”ADC。2022年4月，BAT8009在国内获批临床，拟用于治疗实体肿瘤。 231009 pj D0386 新增作用机制内容 SXZ
XL102 Exelixis 实体瘤 An orally bioavailable, selective inhibitor of cyclin-dependent kinase 7 (CDK7), with potential antineoplastic activity. Upon oral administration, CDK7 inhibitor XL102 selectively targets, covalently binds to and inhibits the activity of CDK7, thereby inhibiting CDK7-mediated signaling. The inhibition of CDK7 prevents phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II, thereby preventing transcription of important cancer-promoting genes. It prevents phosphorylation of the cell cycle kinases CDK1, 2, 4, and 6, thereby disrupting uncontrolled cell cycle progression. Altogether, this may induce apoptosis, cause cell cycle arrest, inhibit DNA damage repair and inhibit tumor cell proliferation in certain cancers that are dependent on CDK7-mediated transcriptional regulation and signaling. CDK7, a serine/threonine kinase, plays a role in controlling cell cycle progression, transcriptional regulation, and promotes the expression of key oncogenes through the phosphorylation of RNA polymerase II. It's overexpressed in multiple cancers. XL102 是一种口服细胞周期蛋白依赖性激酶 7（CDK7）选择性抑制剂，具有潜在的抗肿瘤活性。口服 CDK7 抑制剂 XL102 可选择性地靶向、共价结合并抑制 CDK7 的活性，从而抑制 CDK7 介导的信号传导。抑制 CDK7 可阻止 RNA 聚合酶 II 羧基末端结构域 (CTD) 的磷酸化，从而阻止重要促癌基因的转录。它还能阻止细胞周期激酶 CDK1、2、4 和 6 的磷酸化，从而破坏不受控制的细胞周期进程。在某些依赖 CDK7 介导的转录调控和信号传导的癌症中，CDK7 可诱导细胞凋亡、导致细胞周期停滞、抑制 DNA 损伤修复和抑制肿瘤细胞增殖。CDK7 是一种丝氨酸/苏氨酸激酶，通过磷酸化 RNA 聚合酶 II，在控制细胞周期进展、转录调控和促进关键癌基因表达方面发挥作用。它在多种癌症中过度表达。 XL102是Exelixis公司从Aurigene公司引进的一种选择性、口服生物可利用的共价CDK7抑制剂。已公布的XL102治疗晚期实体肿瘤的1期临床试验初步数据显示：截至2022年9月7日，26例患者接受了XL102治疗，其中1例乳腺癌患者和1例脂肪肉瘤患者达到疾病稳定（SD）。此外，XL102在评估的剂量水平下耐受性良好。 231009 pj D0391 新增作用机制内容 SXZ
Tarloxotinib Rain Therapeutics 非小细胞肺癌 Tarloxotinib is a hypoxia-activated prodrug of a pan-ErbB kinase inhibitor that releases a potent irreversible active metabolite (tarloxotinib-E) under hypoxic conditions to preferentially deliver the active moiety to tumor versus normal tissues. Tarloxotinib是一种泛ErbB激酶抑制剂的缺氧激活原药，在缺氧条件下会释放出一种强效的不可逆活性代谢物（tarloxotinib-E），从而将活性分子优先输送到肿瘤组织而不是正常组织。 Tarloxotinib是一种低氧激活的pan-HER激酶抑制剂，能够在病理生理缺氧情况下释放Tarloxotinib-E，后者对EGFR ex20ins NSCLC也有一定疗效获益潜力。 231009 pj D0394 新增作用机制内容 SXZ
Becotatug 贝柯妥塔单抗 津曼特生物 非小细胞肺癌、食管鳞癌 A human immunoglobulin G1 (IgG1) monoclonal antibody directed against human epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Upon administration, becotatug targets, binds to and prevents the activation of EGFR. This inhibits EGFR-mediated signaling and proliferation of EGFR-expressing tumor cells. In addition, JMT101 may induce antibody-dependent cell-mediated cytotoxicity (ADCC) against EGFR-expressing tumor cells. EGFR, a member of the epidermal growth factor receptor family, is overexpressed on various tumor cell types. Becotatug (JMT101)是一种针对人类表皮生长因子受体（EGFR）的人类免疫球蛋白 G1（IgG1）单克隆抗体，具有潜在的抗肿瘤活性。给药后，becotatug 可靶向、结合并阻止表皮生长因子受体的活化。这将抑制表皮生长因子受体介导的信号传导和表达表皮生长因子受体的肿瘤细胞的增殖。此外，JMT101 还能诱导针对表皮生长因子受体表达肿瘤细胞的抗体依赖性细胞介导的细胞毒作用（ADCC）。表皮生长因子受体（EGFR）是表皮生长因子受体家族的成员之一，在多种肿瘤细胞中过度表达。 JMT101是一款专门治疗EGFR ex20in突变型患者的人源化EGFR单克隆抗体创新药物，属于进行了相关结构优化的第二代抗体药物，对糖基化末端进行了相关修饰，相比目前已获批的西妥昔单抗等，药物亲和力提高了近6倍，抗肿瘤活性明显提升。 231008 pj D0395 新增作用机制内容 SXZ
BDTX-1535 Black Diamond Therapeutics 非小细胞肺癌、胶质母细胞瘤 An orally bioavailable, brain penetrating, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, mutant-selective EGFR inhibitor BDTX-1535 selectively targets, irreversibly binds to, and inhibits the activity of various EGFR alterations and mutations, including certain intrinsic and acquired resistance mutations. This prevents EGFR-mediated signaling in susceptible tumor cells. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. BDTX-1535 是一种口服活性、脑穿透性、突变选择性表皮生长因子受体（EGFR）抑制剂，具有潜在的抗肿瘤活性。口服后，突变选择性表皮生长因子受体抑制剂 BDTX-1535 可选择性地靶向、不可逆地结合并抑制各种表皮生长因子受体改变和突变的活性，包括某些固有和获得性抗性突变。这就阻止了易感肿瘤细胞中表皮生长因子受体介导的信号转导。这既可诱导细胞死亡，也可抑制表皮生长因子受体过表达肿瘤细胞的肿瘤生长。表皮生长因子受体是一种在许多肿瘤细胞类型中发生突变的受体酪氨酸激酶，在肿瘤细胞增殖和肿瘤血管形成中起着关键作用。 BDTX-1535是一种泛EGFR抑制剂，临床前研究显示可以抑制超50种在非小细胞肺癌和胶质母细胞瘤中的致病性EGFR突变以及EGFR扩增。对非小细胞肺癌中的两种常见突变EGFR 19del、L858R的抑制不劣于奥希替尼；对罕见突变如G719X、E709X等的抑制优于奥希替尼；对继发耐药变异如C797S、S768I、G724S、EGFR扩增等的抑制均优于奥希替尼。BDTX-1535相比其他在研4代药的优势是对两种经典EGFR突变和C797S确定性的疗效，以及对各种罕见EGFR突变和EGFR扩增的有效抑制，脑渗透性高，同时毒性较低，既可独当一面也可以作为联药方案的基础，将EGFR靶内突变和脑转移基本全部控制住，再通过其他药物堵靶外突变。 231009 pj D0396 新增作用机制内容 SXZ
Foritinib Succinate 丁二酸复瑞替尼 复星医药 非小细胞肺癌 The succinate salt form of foritinib, an orally bioavailable inhibitor of the receptor tyrosine kinases anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1), with potential antineoplastic activity. Upon oral administration, foritinib targets, binds to and inhibits the activity of ALK and ROS1, which leads to the disruption of ALK- and ROS1-mediated signaling and the inhibition of cell growth in ALK- and ROS1-expressing tumor cells. In addition, foritinib is able to cross the blood brain barrier. ALK and ROS1, overexpressed or mutated in many tumor cell types, play key roles in tumor cell proliferation, survival, invasion and metastasis. Foritinib Succinate (SAF-189s)是foritinib的琥珀酸盐，后者是一种口服生物利用型受体酪氨酸激酶无性淋巴瘤激酶（ALK）和C-ros oncogene 1（ROS1）抑制剂，具有潜在的抗肿瘤活性。口服给药后，foritinib靶向 ALK 和 ROS1，与之结合并抑制其活性，从而破坏 ALK 和 ROS1 介导的信号传导，抑制表达 ALK 和 ROS1 的肿瘤细胞的生长。此外，foritinib还能穿过血脑屏障。ALK和ROS1在许多肿瘤细胞类型中过度表达或突变，在肿瘤细胞增殖、存活、侵袭和转移中发挥关键作用。 SAF-189s（丁二酸复瑞替尼）是由复星医药成员企业江苏万邦开发的新一代ALK和ROS1抑制剂，主要针对ALK或ROS1阳性的非小细胞肺癌。在2022年12月新加坡举办的ESMO ASIA会议上，复星医药公布了SAF-189的1/2期试验结果，其针对ROS1阳性、未经ROS1抑制剂治疗的晚期非小细胞肺癌患者ORR高达85.7%，颅内ORR高达87.5%，展现出令人鼓舞的疗效和良好的安全性。目前非小细胞肺癌（ALK+）适应症在中国已处于III期阶段，并在美国获临床试验批准。 231008 pj D0397 新增作用机制内容，修订药物名称 SXZ
HA121-28 石药集团 非小细胞肺癌、甲状腺髓样癌、胆道癌 An orally available inhibitor of the epidermal growth factor receptor (EGFR), the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET) and vascular endothelial growth factor receptor (VEGFR), with potential anti-angiogenic and antineoplastic activities. Upon oral administration of HA121-28, this agent targets, binds to and inhibits the activity of EGFR, RET and VEGFR. This prevents EGFR-, RET- and VEGFR-mediated signaling, and may lead to the induction of apoptosis and inhibition of tumor growth in EGFR-, RET- and VEGFR-overexpressing cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. Dysregulation of RET activity plays a key role in the development and progression of a variety of cancers. Expression of VEGFR is upregulated in a variety of tumor cell types; it plays a key role in the migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and tumor cell death. HA121-28是一种可口服的表皮生长因子受体（EGFR）、转染过程中重排的原癌基因受体酪氨酸激酶（RET）和血管内皮生长因子受体（VEGFR）抑制剂，具有潜在的抗血管生成和抗肿瘤活性。口服 HA121-28 后，该制剂可靶向、结合并抑制表皮生长因子受体、RET 和血管内皮生长因子受体的活性。这可防止表皮生长因子受体、RET 和血管内皮生长因子受体介导的信号传导，并可诱导表皮生长因子受体、RET 和血管内皮生长因子受体过表达细胞凋亡和抑制肿瘤生长。表皮生长因子受体是一种在许多肿瘤细胞类型中发生突变的受体酪氨酸激酶，在肿瘤细胞增殖和肿瘤血管形成中起着关键作用。RET 活性失调在多种癌症的发生和发展中起着关键作用。血管内皮生长因子受体（VEGFR）的表达在多种肿瘤细胞类型中上调；它在内皮细胞的迁移、增殖和存活、微血管形成、抑制肿瘤细胞增殖和肿瘤细胞死亡中起着关键作用。 HA121-28是石药集团自主研发的1类创新药，是一个新型多靶点酪氨酸激酶抑制剂，能够在细胞水平抑制EGFR、VEGFR和RET及其信号传导通路。在动物药效试验中，对食道癌、甲状腺癌和胃癌均具有良好的治疗效果。 231009 pj D0398 新增作用机制内容 SXZ
GH35 勤浩医药 实体瘤 An orally bioavailable irreversible inhibitor of the oncogenic KRAS substitution mutation, G12C, with potential antineoplastic activity. Upon oral administration, KRAS G12C inhibitor GH35 selectively targets, binds to and inhibits the activity of the KRAS G12C mutant, thereby inhibiting KRAS G12C mutant-dependent signaling. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis. GH35 是一种具有潜在抗肿瘤活性的口服不可逆抑制剂，用于抑制致癌 KRAS G12C 基因突变。口服后，KRAS G12C 抑制剂 GH35 可选择性地靶向、结合并抑制 KRAS G12C 突变的活性，从而抑制依赖于 KRAS G12C 突变的信号转导。KRAS 是 RAS 致癌基因家族的成员，在细胞信号传导、分裂和分化中发挥着重要作用。KRAS 突变可诱导组成型信号转导，导致肿瘤细胞生长、增殖、侵袭和转移。 GH35是一款KRASG12C抑制剂。临床前体内外实验均表明，GH35对KRAS G12C突变具有高选择性和极强的生物活性，对野生型KRAS以及安全性相关的靶点无显著影响，脱靶风险低；同时代谢性质优异，口服生物利用度高，且安全性良好，具有较大的安全窗。目前正在进行Ⅰ期临床试验招募入组肺癌、结直肠癌、胰腺癌的KRAS G12C患者。 231009 pj D0399 新增作用机制内容 SXZ
FCN-437 复星医药 乳腺癌 An orally bioavailable inhibitor of cyclin-dependent kinase (CDK) types 4 (CDK4) and 6 (CDK6), with potential antineoplastic activity. Upon administration, CDK4/6 inhibitor FCN-437 selectively inhibits CDK4 and CDK6, which inhibits the phosphorylation of retinoblastoma protein (Rb) early in the G1 phase, prevents CDK-mediated G1/S transition and leads to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play key roles in the regulation of both cell cycle progression from the G1-phase into the S-phase and cell proliferation. FCN-437 是一种可口服的细胞周期蛋白依赖性激酶（CDK）4（CDK4）和 6（CDK6）抑制剂，具有潜在的抗肿瘤活性。给药后，CDK4/6 抑制剂 FCN-437 可选择性地抑制 CDK4 和 CDK6，从而在 G1 期早期抑制视网膜母细胞瘤蛋白（Rb）的磷酸化，阻止 CDK 介导的 G1/S 转换，导致细胞周期停滞。这就抑制了 DNA 复制，减少了肿瘤细胞的增殖。CDK4 和 6 是丝氨酸/苏氨酸激酶，在许多肿瘤细胞类型中上调，在细胞周期从 G1 期进入 S 期和细胞增殖的调节过程中发挥关键作用。 FCN-437c是一种口服、强效、高选择性、全新结构的CDK4/6抑制剂，数据显示，FCN-437c联合来曲唑客观缓解率（ORR）达到53.6%，且初步安全性数据良好。目前FCN-437c已在国内处于临床III期阶段，在美国处于临床I期。 231009 pj D0400 新增作用机制内容 SXZ
IMP7068 英派药业 实体瘤 An orally bioavailable inhibitor of the human tyrosine kinase Wee1 (Wee1-like protein kinase; Wee1A kinase; WEE1hu), with potential antineoplastic activity. Upon oral administration, Wee1 kinase inhibitor IMP7068 targets, binds to and inhibits Wee1. Inhibition of Wee1 inhibits Cdk1 (Cdc2) phosphorylation, promotes both premature mitosis and a prolonged mitotic arrest, which results in the accumulation of unrepaired DNA damage. This leads to apoptosis in susceptible tumor cells, such as p53-deficient or mutated human cancers that lack the G1 checkpoint. Unlike normal cells, most p53-deficient or mutated human cancers lack the G1 checkpoint as p53 is the key regulator of the G1 checkpoint and these cells rely on the G2 checkpoint for DNA repair to damaged cells. Overexpression of Wee1 occurs in several cancer types and high expression of Wee1 is associated with poor outcomes. Wee1 phosphorylates Cdc2 in the Cdc2/cyclin B (CDK1/cyclin B) complex which blocks progression from G2 into mitosis. The Wee1 tyrosine kinase is activated upon DNA damage and regulates the G2-M and S cell cycle checkpoints. IMP7068 是一种口服的人类酪氨酸激酶 Wee1（Wee1 样蛋白激酶；Wee1A 激酶；WEE1hu）抑制剂，具有潜在的抗肿瘤活性。口服后，Wee1 激酶抑制剂 IMP7068 靶向、结合并抑制 Wee1。抑制 Wee1 可抑制 Cdk1（Cdc2）磷酸化，促进有丝分裂过早和有丝分裂停滞时间延长，从而导致未修复的 DNA 损伤累积。这就导致了易感肿瘤细胞的凋亡，如缺乏 G1 检查点的 p53 缺失或突变人类癌症。与正常细胞不同，大多数 p53 缺乏或突变的人类癌症缺乏 G1 检查点，因为 p53 是 G1 检查点的关键调节因子，而这些细胞依赖 G2 检查点对受损细胞进行 DNA 修复。Wee1在几种癌症类型中都会出现过表达，Wee1的高表达与不良预后有关。Wee1 可使 Cdc2/细胞周期蛋白 B（CDK1/细胞周期蛋白 B）复合物中的 Cdc2 磷酸化，从而阻止细胞从 G2 进入有丝分裂。Wee1 酪氨酸激酶在 DNA 损伤时被激活，并调节 G2-M 和 S 细胞周期检查点。 IMP7068是英派药业自主研发的Wee1抑制剂，动物实验显示，它在动物体内的半衰期及药物暴露量均优于同类在研药物，有望成为best-in-class的药物。2022年9月，公司在2022 ESMO上公布IMP7068在晚期实体瘤患者中的安全性、药代动力学和药效学特征的初步数据，显示在8个爬坡队列中纳入的32例患者，中位随访时间为212天，其中一例患者（子宫浆液性癌）最佳疗效评估达到部分缓解。与研究药物相关的不良事件发生率为65.6%，大多数为1-2级不良事件。说明IMP7068具有良好的耐受性和对WEE1的抑制作用，其药代动力学和药效学特征与剂量水平一致。 231009 pj D0406 新增作用机制内容 SXZ
Batoprotafib 诺华 实体瘤、结直肠癌 Batoprotafib (TNO155) 是一种有效的，选择性的，和具有口服活性野生型 SHP2 的变构抑制剂 (IC50= 0.011 μM)。Batoprotafib 有研究 RTK 依赖性恶性肿瘤的潜力，尤其是晚期实体瘤。 TNO155是诺华开发的一款First-in-class选择性、变构、口服SHP2抑制剂，同时也是首个进入临床的SHP2抑制剂，是在高通量筛选出的先导化合物SHP836的基础上，进一步优化得到的，具有理想的成药性，例如：高渗透性、高溶解度、不抑制CYP450、理想的临床前PK参数。本次TNO155在国内获批临床，拟用于晚期实体瘤。 231008 pj D0409 新增作用机制内容，新增中文名称（Batoprotafib：An inhibitor of protein tyrosine phosphatase (PTP) non-receptor type 11 (SHP2; src homology region 2 domain phosphatase; PTPN11), with potential antineoplastic activity. Upon oral administration,batoprotafib binds to and inhibits SHP2. This prevents SHP2-mediated signaling, inhibits MAPK signaling and prevents growth of SHP2-expressing tumor cells. SHP2, an oncoprotein overexpressed in a variety of cancer cell types, regulates cell survival, differentiation and proliferation through activation of the RAS-RAF-ERK signaling pathway. SHP2 also regulates programmed cell death 1 (PD-1)-mediated signal transduction and is involved in immune checkpoint modulation） SXZ
Trastuzumab Vedotin 乐普生物 乳腺癌、尿路上皮癌、胆管癌、胃癌、胃食管结合部癌、非小细胞肺癌、实体瘤 An antibody-drug conjugate (ADC) composed of trastuzumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against the tumor-associated antigen (TAA) human epidermal growth factor receptor 2 (EGFR2; HER2; ErbB2), conjugated to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration of trastuzumab vedotin, the trastuzumab moiety targets and binds to HER2 on the surface of tumor cells. Following internalization, MMAE targets and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in HER2-expressing tumor cells. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. Trastuzumab Vedotin (MRG002) 是一种由针对肿瘤相关抗原（TAA）人类表皮生长因子受体 2（EGFR2；HER2；ErbB2）的人源化免疫球蛋白 G1（IgG1）单克隆抗体曲妥珠单抗，与微管破坏细胞毒剂单甲基澳瑞他汀 E（MMAE）结合而成的抗体药物共轭物（ADC），具有潜在的抗肿瘤活性。服用 Trastuzumab Vedotin 后，曲妥珠单抗分子会靶向肿瘤细胞表面的 HER2 并与之结合。内化后，MMAE 靶向并与微管蛋白结合，抑制微管聚合。这将导致表达 HER2 的肿瘤细胞进入 G2/M 期细胞周期并凋亡。HER2 是一种酪氨酸激酶受体，在许多癌细胞类型中过度表达。 MRG-002是一款国产DS-8201类似药，由糖修饰曲妥珠单抗通过可酶切vc连接子与MMAE（甲基澳瑞他汀E）偶联而成，在1期临床研究中，HER2阳性多线耐药后的患者，ORR达55%，疗效非常出众，同步也有HER2低表达试验组正在进行，在DS-8201高昂的价格下，参加此试验组可能是HER2阳性及HER2低表达耐药患者最好的选择。 231009 pj D0419 新增作用机制内容 SXZ
Niraparib and Abiraterone acetate Akeega Janssen Biotech 45149 FDA AKEEGA is a combination of niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor indicated with prednisone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved test for AKEEGA. AKEEGA是一种聚(ADP -核糖)聚合酶(PARP)抑制剂尼拉帕尼(niraparib)和一种CYP17抑制剂—醋酸阿比特龙(abiraterone acetate)的组合，与prednisone一起用于治疗携带有害或疑似有害BRCA突变(BRCAm)转移性去势抵抗性前列腺癌(mCRPC)成年患者。 前列腺癌 Niraparib is an inhibitor of PARP enzymes, including PARP-1 and PARP-2, that play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death. Increased niraparibinduced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patientderived xenograft tumor models with homologous recombination deficiency (HRD) that had either mutated or wild-type BRCA1/2. Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by 17α-hydroxylase activity and 2) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenals [see Warnings and Precautions (5.9)].Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor. Abiraterone decreased serum testosterone and other androgens in patients in the placebo-controlled clinical trial. It is not necessary to monitor the effect of abiraterone on serum testosterone levels. Changes in serum prostate specific antigen (PSA) levels may be observed but have not been shown to correlate with clinical benefit in individual patients.In mouse xenograft models of prostate cancer, the combination of niraparib and abiraterone acetate increased anti-tumor activity when compared to either drug alone. Niraparib是PARP酶的抑制剂，包括PARP-1和PARP-2，在DNA修复中起作用。体外研究表明，尼拉帕尼诱导的细胞毒性可能包括抑制PARP酶活性和增加PARP-DNA复合物的形成，导致DNA损伤、细胞凋亡和细胞死亡。在BRCA1 / 2缺失或不缺失的肿瘤细胞系中观察到尼拉帕尼诱导的细胞毒性增加。在BRCA1/2缺失的人癌细胞系的小鼠异种移植模型和同源重组缺失(HRD)的人患者来源的BRCA1/2突变或野生型异种移植肿瘤模型中，尼拉帕尼降低了肿瘤生长。醋酸阿比特龙在体内转化为阿比特龙，这是一种雄激素生物合成抑制剂，可抑制17 α-羟化酶/ c17,20 -裂解酶(CYP17)。这种酶在睾丸、肾上腺和前列腺肿瘤组织中表达，是雄激素生物合成所必需的。CYP17催化两个连续反应:1)通过17α-羟化酶活性将孕烯醇酮和孕酮转化为17α-羟基衍生物;2)随后通过C17, 20裂解酶活性分别形成脱氢表雄酮(DHEA)和雄烯二酮。DHEA和雄烯二酮是雄激素，是睾酮的前体。阿<E38082>
Tebentafusp-tebn Kimmtrak Immunocore 2022/1/25 FDA KIMMTRAK is a bispecific gp100 peptide-HLA-directed CD3 T cell engager indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. KIMMTRAK是一种双特异性gp100肽-HLA-A*02:01靶向T细胞受体CD3 T细胞结合器，适用于治疗HLA-A*02:01阳性、不可切除或转移性葡萄膜黑色素瘤成人患者 葡萄膜黑色素瘤 Tebentafusp-tebn is a bispecific gp100 peptide-HLA-A*02:01 directed T cell receptor CD3 T cell engager. The TCR arm binds to a gp100 peptide presented by human leukocyte antigen-A*02:01 (HLA-A*02:01) on the cell surface of uveal melanoma tumor cells. In vitro, tebentafusp-tebn bound to HLA-A*02:01-positive uveal melanoma cells and activated polyclonal T cells to release inflammatory cytokines and cytolytic proteins, which results in direct lysis of uveal melanoma tumor cells. Tebentafusp-tebn是一种双特异性gp100肽-HLA-A*02:01靶向T细胞受体CD3 T细胞结合器，TCR臂与葡萄膜黑色素瘤肿瘤细胞表面由人类白细胞抗原-A*02:01（HLA-A*02:01）呈现的gp100肽结合。在体外，tebentafusp-tebn与HLA-A*02:01阳性葡萄膜黑色素瘤细胞结合，激活多克隆T细胞释放炎性细胞因子和细胞溶解蛋白，从而直接裂解葡萄膜黑色素瘤肿瘤细胞。 FDA-approval: 11/2022 230920 pj D0445 新增药物 SXZ
APS03118 APS03118 is a novel next-generation RET inhibitor which is potent against a range of RET fusions and mutations including both SFMs and gatekeeper mutations. APS03118 是一种新型的下一代 RET 抑制剂，对一系列 RET 融合和突变（包括溶剂前沿突变[SFMs]和守门员突变）具有很强的抑制作用。 231007 pj D0455 新增药物 SXZ
ART0380 ART0380 is a potent, selective and orally active inhibitor of ataxia telangiectasia and Rad3-related (ATR) that has been developed for treatment for cancer patients with DNA repair defects. ART0380 是一种强效、选择性和口服的共济失调毛细血管扩张Rad3相关蛋白（ATR）抑制剂，已被开发用于治疗存在 DNA 修复缺陷的癌症患者。 231007 pj D0456 新增药物 SXZ
ERAS-801 ERAS-801 is a highly CNS-penetrant small molecule (Kp, brain, mouse = 3.7 and Kp,uu, brain, mouse = 1.2) designed to reversibly inhibit EGFR alterations observed in GBM, including EGFR amplification and the EGFRvIII variant. It is currently being evaluated in recurrent GBM in the phase 1 clinical trial THUNDERBBOLT-1 (NCT05222802). ERAS-801 also shows in vitro activity against other EGFR alterations observed in NSCLC. ERAS-801 是一种高度中枢神经系统（CNS）穿透性的小分子（Kp，脑，小鼠=3.7；Kp,uu，脑，小鼠=1.2），旨在可逆地抑制在胶质母细胞瘤（ GBM）中观察到的表皮生长因子受体（EGFR）变异，包括 EGFR 扩增和 EGFR vIII 突变。目前，1 期临床试验ENDERBBOLT-1（NCT05222802）正在对该药在复发性 GBM 中的应用进行评估。ERAS-801 对 NSCLC 中观察到的其他EGFR突变也有体外活性。 231007 pj D0457 新增药物 SXZ
Evorpacept Evorpacept is a highly differentiated anti-CD47 blocker with an inactive Fc effector function. In clinical studies evorpacept has demonstrated a substantially better safety profile to date than competing anti-CD47 molecules with an active Fc. Evorpacept 是新一代免疫检查点抑制剂，作为一种高度差异化的抗 CD47 阻断剂，具有非活性 Fc 效应功能。迄今为止，在临床研究中，Evorpacept 的安全性大大优于其他具有活性 Fc 的抗 CD47 分子。 231007 pj D0458 新增药物 SXZ
Onvansertib Onvansertib (PCM-075) is a novel, orally available PLK1 inhibitor, which shows tumor growth inhibition in various types of cancer. Onvansertib是一种新型口服丝氨酸/苏氨酸polo样激酶1（PLK1）抑制剂，对多种类型的癌症具有抑制肿瘤生长的作用。 231007 pj D0459 新增药物 SXZ
pertuzumab/ trastuzumab and hyaluronidase-zzxf 帕妥珠单抗/曲妥珠单抗/透明质酸酶-zzxf Phesgo 基因泰克 44011 FDA PHESGO is a combination of pertuzumab and trastuzumab, HER2/neu receptor antagonists, and hyaluronidase, an endoglycosidase, indicated for: ? Use in combination with chemotherapy as: o neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. o adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence. ? Use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. PHESGO 是帕妥珠单抗和曲妥珠单抗（一种HER2/neu受体拮抗剂）以及透明质酸酶（一种糖苷内切酶）的复方制剂，适用于：1. 联合化疗用于：1）作为早期乳腺癌完全治疗方案的一部分，对HER2阳性、局部晚期、炎性或早期乳腺癌（直径大于2cm或结节阳性）患者进行新辅助治疗；2）对高复发风险的HER2阳性早期乳腺癌患者进行辅助治疗。2. 与多西他赛联合用于治疗既往未接受过抗HER2治疗或转移性疾病化疗的HER2阳性转移性乳腺癌（MBC）患者。 乳腺癌 Pertuzumab targets the extracellular dimerization domain (subdomain II) of HER2 and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3 and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signaling pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. Trastuzumab binds to subdomain IV of the extracellular domain of the HER2 protein to inhibit the ligand-independent, HER2 mediated cell proliferation and PI3K signaling pathway in human tumor cells that overexpress HER2. Both pertuzumab and trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) have been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2. While pertuzumab alone inhibited the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab augmented anti-tumor activity in HER2-overexpressing xenograft models. Hyaluronan is a polysaccharide found in the extracellular matrix of the subcutaneous tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a half-life of approximately 0.5 days. Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizing hyaluronan. In the doses administered, hyaluronidase in PHESGO acts transiently and locally. The effects of hyaluronidase are reversible and permeability of the subcutaneous tissue is restored within 24 to 48 hours. Hyaluronidase has been shown to increase the absorption rate of a trastuzumab product into the systemic circulation when given in the subcutis of G?ttingen Minipigs. 帕妥珠单抗（pertuzumab）以HER2的胞外二聚化结构域（亚域II）为靶点，从而阻断HER2与其他HER家族成员（包括EGFR、HER3和HER4）的配体依赖性异源二聚化。因此，帕妥珠单抗可抑制配体通过两种主要信号通路（丝裂原活化蛋白激酶[MAP]和磷脂酰肌酸激酶[PI3K]）引发的细胞内信号转导。抑制这些信号通路可分别导致细胞生长停滞和细胞凋亡。曲妥珠单抗能与HER2蛋白胞外域的亚域IV结合，抑制HER2介导的细胞增殖和PI3K信号通路，从而抑制HER2过表达的人类肿瘤细胞中与配体无关的细胞增殖和PI3K信号通路。与不过表达HER2的癌细胞相比，帕妥珠单抗和曲妥珠单抗介导的抗体依赖性细胞介导的<E5AFBC><E79A84>
VT3989 VT3989 is an oral, highly potent and selective inhibitor of TEAD palmitoylation, which blocks YAP function and has shown promising preclinical activity. VT3989 是一种口服、高效、选择性的转录增强缔合域（TEAD）棕榈酰化抑制剂，可阻断yes相关蛋白（YAP）的功能，并已显示出良好的临床前活性。 231007 pj D0461 新增药物 SXZ
ACT001 尚德药缘 实体瘤、肺癌、胶质瘤 The fumarate salt form of the parthenolide derivative micheliolide (MCL), and an orally bioavailable guaianolide sesquiterpene lactone and inhibitor of the protease plasminogen activator inhibitor-1 (PAI-1), with potential immunomodulating and antineoplastic activities. Upon oral administration, PAI-1 inhibitor ACT001 targets and binds to PAI-1, thereby inhibiting the PAI-1/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. This induces apoptosis in and inhibits the proliferation, migration and invasion of tumor cells in which the PI3K/AKT pathway is overexpressed. In addition, ACT001 binds to and inhibits the activity of inhibitor of nuclear factor kappa-B kinase subunit beta (IKK-beta), thereby inhibiting nuclear factor kappa B (NF-kB) signaling. This leads to the downregulation of manganese superoxide dismutase (MnSOD) and induces the generation of reactive oxygen species (ROS). This induces G2/M phase arrest and tumor cell apoptosis. Also, ACT001 binds to and inhibits the phosphorylation of signal transducer and activator of transcription 3 (STAT3), and reduces the expression of programmed death-ligand 1 (PD-L1). This may modulate the anti-tumor immune response. ACT001 may also affect tissue remodeling and cancer metabolism. PAI-1 plays a key role in the proliferation, migration, invasion and adhesion of cancer cells as well as multidrug resistance. It is highly expressed in certain tumors, such as gliomas. ACT001 is able to cross the blood-brain barrier (BBB). ACT001是一种小白菊内酯衍生物micheliolide (MCL)的富马酸盐形式，是具有口服生物活性的愈创木烷型倍半萜内酯，且为纤溶酶原激活物抑制剂1（PAI-1）抑制剂，具有潜在免疫调节和抗肿瘤活性。口服 PAI-1 抑制剂 ACT001 可靶向并结合 PAI-1，从而抑制 PAI-1/磷酸肌醇 3- 激酶（PI3K）/蛋白激酶 B（AKT）通路。这将诱导 PI3K/AKT 通路过度表达的肿瘤细胞凋亡，并抑制其增殖、迁移和侵袭。此外，ACT001 还能与核因子κ-B 激酶亚基 β 抑制剂（IKK-β）结合并抑制其活性，从而抑制核因子κ-B（NF-κB）信号传导。这导致锰超氧化物歧化酶（MnSOD）的下调，并诱导活性氧（ROS）的产生。这将诱导 G2/M 期停滞和肿瘤细胞凋亡。此外，ACT001 还能与信号转导和激活转录 3（STAT3）结合并抑制其磷酸化，减少程序性死亡配体 1（PD-L1）的表达。这可能会调节抗肿瘤免疫反应。ACT001 还可能影响组织重塑和癌症代谢。PAI-1 在癌细胞的增殖、迁移、侵袭和粘附以及多药耐药性方面起着关键作用。它在某些肿瘤（如胶质瘤）中高度表达。ACT001 能够穿过血脑屏障（BBB）。 ACT001是一种多靶点小分子免疫调节剂，能够很好地穿过血脑屏障，并且能够可逆地开放血脑屏障，帮助其它药物提高入脑浓度，因此ACT001可用于颅内疾病的治疗。ACT001是草药活性物质小白菊内酯的结构优化产物，以小白菊内酯为原料，通过三步化学反应合成而来。 231009 pj D0462 新增药物 SXZ
AL2846 正大天晴 非小细胞肺癌 An orally bioavailable small molecule inhibitor of the oncoprotein c-Met (hepatocyte growth factor receptor; HGFR), with potential antineoplastic activity. Upon oral administration AL2846 targets and binds to the c-Met protein, prevents c-Met phosphorylation and disrupts c-Met-dependent signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis. AL2846 是一种口服小分子肿瘤蛋白 c-Met（肝细胞生长因子受体；HGFR）抑制剂，具有潜在的抗肿瘤活性。口服 AL2846 可靶向结合 c-Met 蛋白，阻止 c-Met 磷酸化，破坏依赖于 c-Met 的信号转导途径。c-Met 蛋白在许多肿瘤细胞类型中过度表达或突变，在肿瘤细胞增殖、存活、侵袭、转移和肿瘤血管生成中发挥关键作用。 AL2846是一种c-Met抑制剂，拟用于胃癌、乳腺癌、结肠癌和肾细胞癌等疾病的治疗。作为特殊审批品种的1.1类新药，AL2846目前已在国内开展4项试验，分别针对晚期非小细胞肺癌、晚期恶性肿瘤、晚期结直肠癌和晚期胰腺癌。 231009 pj D0463 新增药物 SXZ
ARX517 Ambrx 前列腺癌 An antibody-drug conjugate (ADC) containing a humanized immunoglobulin G1 kappa (IgG1k) monoclonal antibody directed against prostate-specific membrane antigen (PSMA) and site-specifically conjugated to two of the microtubule-disrupting toxin amberstatin (AS269), with potential antineoplastic activity. Upon administration of anti-PSMA ADC ARX517, the monoclonal antibody moiety selectively binds to PSMA, a protein which is abundantly expressed on the surface of metastatic and hormone-refractory prostate cancer cells. Upon internalization, amberstatin binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. The site-specific conjugation of the cytotoxic agent to the antibody improves the biophysical properties of ARX517, increases payload stability and optimizes its efficacy. ARX517 是一种抗体-药物共轭物（ADC）含有针对前列腺特异性膜抗原（PSMA）的人源化免疫球蛋白 G1 κ（IgG1κ）单克隆抗体，并与两种微管破坏毒素琥珀肽（AS269）定点结合，具有潜在的抗肿瘤活性。服用抗 PSMA ADC ARX517 后，单克隆抗体分子会选择性地与 PSMA 结合，PSMA 是一种在转移性和激素难治性前列腺癌细胞表面大量表达的蛋白质。内化后，琥珀肽与微管蛋白结合并抑制其聚合，导致 G2/M 期停滞和肿瘤细胞凋亡。细胞毒剂与抗体的特异性位点共轭改善了 ARX517 的生物物理特性，提高了有效载荷的稳定性并优化了其药效。 ARX517是Ambrx研发的一款靶向PSMA的ADC，由一个全人源的抗PSMA单抗和两个微管蛋白抑制剂AS269构成。AS269为Ambrx专有的、强效的微管蛋白抑制剂，可与抗体里的合成氨基酸形成高度稳定的共价键。在临床前试验中，ARX517在恩扎卢胺敏感性和耐药性前列腺癌模型中展现出活性。2023年7月19日，Ambrx公司宣布ARX517获批FDA快速通道（FTD）资格，用于治疗雄激素受体通路抑制剂治疗后进展的转移性去势抵抗性前列腺癌（mCRPC）患者。 231009 pj D0464 新增药物 SXZ
ERAS-601 Erasca 非小细胞肺癌、实体瘤 An orally bioavailable inhibitor of protein tyrosine phosphatase (PTP) non-receptor type 11 (SHP2; Src homology region 2 domain phosphatase; PTPN11), with potential antineoplastic activity. Upon oral administration, SHP2 inhibitor ERAS-601 targets, binds to and inhibits the activity of SHP2. This prevents SHP2-mediated signaling, inhibits MAPK signaling and prevents growth of SHP2-expressing tumor cells. SHP2, an oncoprotein overexpressed in a variety of cancer cell types, regulates cell survival, differentiation and proliferation through activation of the Ras-Raf-MEK-ERK signaling pathway. The Ras-MAPK pathway is often hyperactivated in cancer cells due to specific mutations and rearrangements which are dependent on SHP2 for their oncogenic signaling. SHP2 also regulates programmed cell death 1 (PD-1)-mediated signal transduction and is involved in immune checkpoint modulation. ERAS-601 是一种口服活性蛋白酪氨酸磷酸酶（PTP）非受体型 11（SHP2；Src 同源区域 2 结构域磷酸酶；PTPN11）抑制剂，具有潜在的抗肿瘤活性。口服后，SHP2 抑制剂 ERAS-601 可靶向、结合并抑制 SHP2 的活性。这样就能阻止 SHP2 介导的信号传导，抑制 MAPK 信号传导，防止表达 SHP2 的肿瘤细胞生长。SHP2是一种在多种癌细胞类型中过度表达的肿瘤蛋白，它通过激活Ras-Raf-MEK-ERK信号通路来调节细胞的存活、分化和增殖。在癌细胞中，Ras-MAPK 通路通常会因特定的突变和重排而被过度激活，而这些细胞的致癌信号则依赖于 SHP2。SHP2 还能调节由程序性细胞死亡 1（PD-1）介导的信号转导，并参与免疫检查点调节。 ERAS-601是一种潜在的同类最佳的口服选择性SHP2抑制剂，从NiKang引进。2022年Erasca宣布了其ERK1/2抑制剂ERAS-007和ERAS-601在BRAF驱动和RAS/MAPK改变的实体肿瘤中积极的初步1/1b期临床试验数据：23%（6/26）RAS/MAPK改变的非结直肠癌（CRC）实体肿瘤患者和44%（4/9）BRAF驱动的非CRC实体肿瘤患者对单药ERAS-007或ERAS-601有反应（包括已确认和未确认的PR）。而且，这两种药物具有良好的安全性和耐受性，且与治疗相关的不良事件基本不重叠，支持药物联用的开发。此外，2022年7月，Erasca与礼来达成临床试验合作和供应协议，评估ERAS-601和西妥昔单抗的组合疗法。 231009 pj D0467 新增药物 SXZ
GQ1001 启德医药 实体瘤 An antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (EGFR2; HER2; ErbB2) and conjugated, via a site-specific linker, to the cytotoxic maytansinoid mertansine (DM1), with potential antineoplastic activity. Upon administration of anti-HER2-DM1 ADC GQ1001, the antibody moiety targets and binds to HER2 on tumor cell surfaces. Upon cellular uptake and internalization, DM1 binds to tubulin and interferes with microtubule assembly and disassembly dynamics. This inhibits cell division and the proliferation of tumor cells that overexpress HER2. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. GQ1001 是一种抗体药物共轭物（ADC），由靶向人类表皮生长因子受体 2（EGFR2；HER2；ErbB2）的单克隆抗体和具有潜在抗肿瘤活性的细胞毒性 Mertansine（DM1）通过特异性位点连接体共轭而成。服用抗 HER2-DM1 ADC GQ1001 后，抗体分子会与肿瘤细胞表面的 HER2 靶向结合。细胞吸收和内化后，DM1 会与微管蛋白结合，干扰微管的组装和分解动力学。这就抑制了细胞分裂和过度表达 HER2 的肿瘤细胞的增殖。HER2 是一种酪氨酸激酶受体，在许多癌细胞类型中都有过表达。 GQ1001是根据连接酶催化偶联技术和开环连接子技术，通过毒素DM1与trastuzumab的定点特异性偶联产生的ADC，目前在全球多中心临床试验中用于治疗 HER2+实体瘤。 231009 pj D0468 新增药物 SXZ
MCLA-129 Merus 非小细胞肺癌 A human bispecific immunoglobulin G1 (IgG1) antibody targeting the tumor-associated antigens (TAAs) epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR; c-Met), with potential antineoplastic activity. Upon administration, anti-EGFR/c-Met bispecific antibody MCLA-129 simultaneously targets and binds to the extracellular domains of both EGFR and c-Met expressed on cancer cells. This prevents the activation of both EGFR- and c-Met-mediated signaling pathways. The binding results in antibody-dependent cellular cytotoxicity (ADCC), thereby inhibiting tumor cell proliferation and survival. EGFR and c-Met, both upregulated or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation. MCLA-129 是一种靶向肿瘤相关抗原（TAAs）表皮生长因子受体（EGFR）和肝细胞生长因子受体（HGFR；c-Met）的人类双特异性免疫球蛋白 G1（IgG1）抗体，具有潜在的抗肿瘤活性。给药后，抗 EGFR/c-Met 双特异性抗体 MCLA-129 可同时靶向并结合癌细胞上表达的 EGFR 和 c-Met 的胞外域。这就阻止了 EGFR 和 c-Met 介导的信号通路的激活。这种结合会产生抗体依赖性细胞毒性（ADCC），从而抑制肿瘤细胞的增殖和存活。EGFR 和 c-Met 在多种肿瘤细胞类型中均上调或突变，在肿瘤细胞增殖中发挥着关键作用。 MCLA-129是一款针对表皮生长因子受体（EGFR）和细胞间质上皮转化因子（c-Met）双靶点的双特异性抗体，可同时阻断EGFR和c-Met的信号传导，抑制肿瘤的生长和存活，且可经增强的抗体依赖的细胞介导的细胞毒性作用（ADCC）进一步提高对肿瘤细胞的杀伤潜能。其拟用于“EGFR或MET异常的晚期实体瘤患者的治疗”的临床试验正在开展。 231009 pj D0469 新增药物 SXZ
SPH4336 上海医药 实体瘤、脂肪肉瘤 An orally bioavailable selective inhibitor of cyclin-dependent kinase (CDK) types 4 (CDK4) and 6 (CDK6), with potential antineoplastic activity. Upon oral administration, CDK4/6 inhibitor SPH4336 selectively targets and inhibits the activity of CDK4 and CDK6, which inhibits the phosphorylation of retinoblastoma protein (Rb) early in the G1 phase, prevents CDK-mediated G1-S-phase transition and leads to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of both cell cycle progression from the G1-phase into the S-phase and tumor cell proliferation. SPH4336 是一种口服的选择性细胞周期蛋白依赖性激酶（CDK）4 型（CDK4）和 6 型（CDK6）抑制剂，具有潜在的抗肿瘤活性。口服 CDK4/6 抑制剂 SPH4336 可选择性地靶向 CDK4 和 CDK6 并抑制其活性，从而在 G1 期早期抑制视网膜母细胞瘤蛋白（Rb）的磷酸化，阻止 CDK 介导的 G1-S 期转变并导致细胞周期停滞。这就抑制了 DNA 复制，减少了肿瘤细胞的增殖。CDK4 和 6 是丝氨酸/苏氨酸激酶，在许多肿瘤细胞类型中上调，在细胞周期从 G1 期进入 S 期和肿瘤细胞增殖的调节过程中发挥着关键作用。 SPH4336片是上海医药自主开发的口服小分子抑制剂，对CDK4/6靶点具有较高的选择性，广谱抗Rb阳性肿瘤活性。同时在临床病人来源的脂肪肉瘤PDX的裸小鼠皮下移植瘤模型上，SPH4336显示出显著的抗肿瘤作用。因此预估SPH4336片治疗脂肪肉瘤有一定潜力。目前，SPH4336片针对局部晚期或转移性脂肪肉瘤的Ⅱ期临床试验已获得美国食品药品监督管理局（FDA）批准，并已与临床CRO签署正式协议。在国内，SPH4336片已完成针对晚期实体瘤的I期临床试验，数据显示其具有良好的药效、较高的安全性和优良的药代动力学性质，即将进入中国Ⅰb/Ⅱa期脂肪肉瘤临床研发。 231009 pj D0470 新增药物 SXZ
HRS-4642 恒瑞医药 实体瘤 An inhibitor of the oncogenic KRAS substitution mutation G12D, with potential antineoplastic activity. Upon administration, KRAS G12D inhibitor HRS-4642 specifically targets and binds to KRAS G12D. This prevents KRAS G12D-mediated signaling and activation of downstream survival pathways. This leads to an inhibition of the growth of tumor cells that overexpress KRAS G12D. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell proliferation, invasion, and metastasis. HRS-4642 是一种具有潜在抗肿瘤活性的致癌 KRAS G12D 替代突变抑制剂。给药后，KRAS G12D 抑制剂 HRS-4642 会特异性地靶向并结合 KRAS G12D。这将阻止 KRAS G12D 介导的信号传导和下游生存通路的激活。这将抑制过量表达 KRAS G12D 的肿瘤细胞的生长。KRAS 是 RAS 致癌基因家族的成员，在细胞信号传导、分裂和分化中发挥着重要作用。KRAS 基因突变可诱导组成型信号转导，导致肿瘤细胞增殖、侵袭和转移。 231010 pj D0472 新增药物 SXZ
ELI-002 Elicio A peptide-based cancer vaccine composed of the adjuvant Amphiphile (Amph; AMP)-CpG-7909, which is a lipid-conjugated immune-stimulatory oligonucleotide, admixed with Amph modified Kirsten Rat Sarcoma (KRAS) mutated peptides, which contain a mixture of lipid-conjugated peptide-based antigens, with potential immunostimulatory and antitumor activities. Upon subcutaneous administration of the AMP KRAS vaccine ELI-002, the lipid moieties bind to tissue albumin and the complex is delivered to and accumulates in the lymph nodes where it is taken up by antigen presenting cells (APCs), primarily dendritic cells (DCs). This may stimulate the host immune system to mount a cytotoxic T-cell lymphocyte (CTL)-mediated immune response against KRAS/neuroblastoma ras viral oncogene homolog (NRAS)-expressing tumor cells. KRAS and NRAS, tumor-associated antigens (TAAs) that are involved in the RAS/mitogen-activated protein kinase (MAPK) signaling pathway, are overexpressed on a variety of tumor cell types and play key role in tumor cell proliferation. The CpG-based adjuvant may enhance the mutated KRAS T cell-specific immune response. ELI-002 2P contains two KRAS mutated Amph-peptides, including Amph-G12D and Amph-G12R. ELI-002 (ELI-002 7P) contains seven KRAS mutated Amph-peptides (Amph-Peptide 7), including G12D, G12R, G12V, G12A, G12C, G12S and G13D. ELI-002 是一种基于肽的癌症疫苗，由佐剂Amphiphile (Amph; AMP)-CpG-7909（一种脂质结合的免疫刺激寡核苷酸）与Amph修饰的KRAS突变肽段（含有一种脂质结合的基于肽的抗原混合物）混合组成，具有潜在的免疫刺激和抗肿瘤活性。皮下注射 AMP KRAS 疫苗 ELI-002 后，脂质分子与组织白蛋白结合，复合物被输送到淋巴结并在淋巴结中积聚，被抗原呈递细胞（APC），主要是树突状细胞（DC）吸收。这可能会刺激宿主免疫系统对表达 KRAS/NRAS 的肿瘤细胞产生细胞毒性 T 细胞淋巴细胞（CTL）介导的免疫反应。KRAS 和 NRAS 是肿瘤相关抗原（TAA），它们参与 RAS/MAPK 信号通路，在多种肿瘤细胞类型中过度表达，并在肿瘤细胞增殖中发挥关键作用。基于 CpG 的佐剂可增强突变 KRAS T 细胞特异性免疫反应。ELI-002 2P 含有两种 KRAS 突变的 Amph 肽，包括 Amph-G12D 和 Amph-G12R。ELI-002 (ELI-002 7P)含有七种 KRAS 突变的 Amph 肽（Amph 肽7），包括G12D、G12R、G12V、G12A、G12C、G12S和G13D。 231012 pj D0473 新增药物 SXZ
Ziv-Aflibercept 阿柏西普 Zaltrap 赛诺菲 2012/8/3 FDA ZALTRAP, a vascular endothelial growth factor inhibitor, in combination with fluorouracil, leucovorin, irinotecan (FOLFIRI), is indicated for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed following an oxaliplatin-containing regimen. ZALTRAP是一种血管内皮生长因子抑制剂，联合氟尿嘧啶、亚叶酸、伊立替康（FOLFIRI），用于治疗对含奥沙利铂方案耐药或有进展的转移性结直肠癌患者。 结直肠癌 Ziv-aflibercept acts as a soluble receptor that binds to human VEGF-A (equilibrium dissociation constant KD of 0.5 pM for VEGF-A165 and 0.36 pM for VEGF-A121), to human VEGF-B (KD of 1.92 pM), and to human PlGF (KD of 39 pM for PlGF-2). By binding to these endogenous ligands, ziv-aflibercept can inhibit the binding and activation of their cognate receptors. This inhibition can result in decreased neovascularization and decreased vascular permeability.In animals, ziv-aflibercept was shown to inhibit the proliferation of endothelial cells, thereby inhibiting the growth of new blood vessels. Ziv-aflibercept inhibited the growth of xenotransplanted colon tumors in mice. Ziv-aflibercept作为一种可溶性受体，与人类VEGF-A（VEGF-A165的平衡解离常数KD为0.5pM，VEGF-A121为0.36pM）、人类VEGF-B（KD为1.92 pM）和人类PlGF（PlGF-2的KD为39pM）结合。通过与这些内源性配体结合，Ziv-aflibercept可以抑制其同源受体的结合和激活。这种抑制可导致新生血管的减少和血管通透性降低。在动物中，Ziv-aflibercept可以抑制内皮细胞的增殖，从而抑制新血管的生长。Ziv-aflibercept抑制小鼠异种移植结肠肿瘤的生长。 06/2020 231027 pj D0474 新增药物 SXZ
Birociclib 吡罗西尼 An orally bioavailable selective inhibitor of cyclin-dependent kinase (CDK) types 4 (CDK4) and 6 (CDK6), with potential antineoplastic activity. Upon oral administration, CDK4/6 inhibitor XZP-3287 selectively targets and inhibits the activity of CDK4 and CDK6, which inhibits the phosphorylation of retinoblastoma protein (Rb) early in the G1 phase, prevents CDK-mediated G1-S-phase transition and leads to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of both cell cycle progression from the G1-phase into the S-phase and tumor cell proliferation. Birociclib (XZP-3287) 是一种口服生物可利用型选择性细胞周期蛋白依赖性激酶（CDK）4 型（CDK4）和 6 型（CDK6）抑制剂，具有潜在的抗肿瘤活性。口服 CDK4/6 抑制剂 XZP-3287 可选择性地靶向 CDK4 和 CDK6 并抑制其活性，从而在 G1 期早期抑制视网膜母细胞瘤蛋白（Rb）的磷酸化，阻止 CDK 介导的 G1-S 期转变并导致细胞周期停滞。这就抑制了 DNA 复制，减少了肿瘤细胞的增殖。CDK4 和 6 是丝氨酸/苏氨酸激酶，在许多肿瘤细胞类型中上调，在细胞周期从 G1 期进入 S 期和肿瘤细胞增殖的调节过程中发挥着关键作用。 2023年10月17日，轩竹生物发布新闻稿称：1类新药吡罗西尼（birociclib）的上市申请获得中国国家药品监督管理局（NMPA）受理，针对适应症为：吡罗西尼单药用于既往转移性阶段接受过二种及以上内分泌治疗和一种化疗后出现疾病进展的激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性的局部晚期或转移性成年乳腺癌患者。 231030 pj D0475 新增药物 SXZ
BAY-2927088 An orally bioavailable, mutant-selective, dual kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), with potential antineoplastic activity. Upon oral administration, EGFR/HER2 mutant-selective inhibitor BAY2927088 targets, binds to, and inhibits the activity of EGFR and HER2 with exon20 insertion mutations, as well as EGFR with C797X mutations, thereby preventing EGFR- and HER2-mediated signaling. This may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors. EGFR and HER2 are receptor tyrosine kinases that play major roles in tumor cell proliferation and tumor vascularization. BAY-2927088 是一种口服生物活性、突变选择性表皮生长因子受体（EGFR）和人表皮生长因子受体 2（HER2）双重激酶抑制剂，具有潜在的抗肿瘤活性。口服给药后，EGFR/HER2 突变选择性抑制剂 BAY2927088 可靶向、结合和抑制具有外显子 20 插入突变的 EGFR 和 HER2 以及具有 C797X 突变的 EGFR 活性，从而阻止 EGFR 和 HER2 介导的信号转导。这可能会抑制肿瘤的生长和血管生成，并使表达 EGFR/HER2 的肿瘤消退。EGFR 和 HER2 是受体酪氨酸激酶，在肿瘤细胞增殖和肿瘤血管生成中发挥着重要作用。 231030 pj D0476 新增药物 SXZ
VC004 An orally bioavailable, second-generation tropomyosin-related-kinase (TRK) inhibitor, with potential antineoplastic activity. Upon oral administration, TRK inhibitor VC004 specifically targets and binds to TRK, TRK mutations and fusion proteins containing sequences from neurotrophic tyrosine receptor kinase (NTRK) types 1 (NTRK1; TrkA), 2 (NTRK2; TrkB), and 3 (NTRK3; TrkC). This inhibits neurotrophin-TRK interaction and TRK activation, thereby preventing the activation of downstream signaling pathways, including the PI3K, RAS/MAPK/ERK and PLC-gamma pathways that are activated by these kinases. This results in both the induction of cellular apoptosis and the inhibition of cell growth in tumors that overexpress TRK and/or express NTRK fusion proteins. TRK, a family of receptor tyrosine kinases (RTKs) activated by neurotrophins, is encoded by NTRK family genes. The expression of either mutated forms of, or fusion proteins involving NTRK family members results in uncontrolled TRK signaling, which plays an important role in tumor cell growth, survival, invasion and treatment resistance. VC004 是一种可口服的第二代肌球蛋白相关激酶（TRK）抑制剂，具有潜在的抗肿瘤活性。口服后，TRK 抑制剂 VC004 可特异性地靶向并结合 TRK、TRK 突变体以及含有神经营养酪氨酸受体激酶（NTRK）1 型（NTRK1；TrkA）、2 型（NTRK2；TrkB）和 3 型（NTRK3；TrkC）序列的融合蛋白。这抑制了神经营养素与 TRK 的相互作用和 TRK 的激活，从而阻止了下游信号通路的激活，包括由这些激酶激活的 PI3K、RAS/MAPK/ERK 和 PLC-γ 通路。这样，在过度表达 TRK 和/或表达 NTRK 融合蛋白的肿瘤中，既能诱导细胞凋亡，又能抑制细胞生长。TRK是由神经营养素激活的受体酪氨酸激酶（RTK）家族，由NTRK家族基因编码。NTRK家族成员的突变形式或融合蛋白的表达会导致TRK信号传导失控，从而在肿瘤细胞的生长、存活、侵袭和抗药性方面发挥重要作用。 231030 pj D0477 新增药物 SXZ
Carfilzomib 卡非佐米 Kyprolis 凯洛斯 安进 41110 FDA/NMPA Kyprolis is a proteasome inhibitor that is indicated: for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with o Lenalidomide and dexamethasone; or o Dexamethasone; or o Daratumumab and dexamethasone; or o Daratumumab and hyaluronidase-fihj and dexamethasone; or o Isatuximab and dexamethasone. ? as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. Kyprolis是一种蛋白酶体抑制剂，适用于：1.联合来那度胺和地塞米松，或地塞米松，或达雷妥尤单抗和地塞米松，或达雷妥尤单抗、透明质酸酶-fihj和地塞米松，或伊沙妥昔单抗和地塞米松，用于治疗复发或难治性多发性骨髓瘤成人患者，这些患者接受过一至三种治疗。2. 单药用于治疗接受过一种或多种疗法的复发或难治性多发性骨髓瘤患者。2021年，NMPA批准卡非佐米上市，本品与地塞米松联合适用于治疗复发或难治性多发性骨髓瘤成人患者，患者既往至少接受过2种治疗，包括蛋白酶体抑制剂和免疫调节剂。 多发性骨髓瘤 Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. Carfilzomib had antiproliferative and proapoptotic activities in vitro in solid and hematologic tumor cells. In animals, carfilzomib inhibited proteasome activity in blood and tissue and delayed tumor growth in models of multiple myeloma, hematologic, and solid tumors. 卡非佐米（Carfilzomib）是一种四肽环氧酮蛋白酶体抑制剂，能不可逆地与20S蛋白酶体（26S蛋白酶体中的蛋白水解核心颗粒）的N端含苏氨酸的活性位点结合。卡非佐米在体外对实体瘤和血液肿瘤细胞具有抗增殖和促凋亡活性。在动物身上，卡非佐米可抑制血液和组织中蛋白酶体的活性，并延缓多发性骨髓瘤、血液肿瘤和实体瘤模型中肿瘤的生长。 06/2022 231030 pj D0479 新增药物 SXZ
IMA203 A preparation of autologous T-lymphocytes that are genetically modified with a lentiviral vector encoding a T-cell receptor (TCR) specific for the tumor-associated antigen (TAA) preferentially expressed antigen in melanoma (PRAME), with potential antineoplastic activity. Upon intravenous administration back into the patient, the autologous PRAME-targeting TCR-engineered T-cells IMA203 specifically recognize and bind to PRAME expressed on cancer cells, which induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against the PRAME-expressing cancer cells. PRAME is overexpressed by a variety of cancer cell types. IMA203 是一种具有潜在抗肿瘤活性的自体T淋巴细胞制剂，这种自体T淋巴细胞用慢病毒载体进行了基因修饰，该载体编码针对黑色素瘤中优先表达的肿瘤相关抗原（TAA）的特异性T细胞受体（TCR）。静脉注射回患者体内后，自体 PRAME 靶向 TCR 工程 T 细胞 IMA203 能特异性识别癌细胞上表达的 PRAME 并与之结合，从而诱导细胞毒性 T 淋巴细胞（CTL）介导的针对 PRAME 表达癌细胞的免疫反应。各种类型的癌细胞都会过量表达 PRAME。 231030 pj D0481 新增药物 SXZ
LM-302 An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against the tumor-associated antigen (TAA) claudin 18.2 (CLDN18.2; A2 isoform of claudin-18) conjugated via a cleavable linker, to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, anti-CLDN18.2 ADC LM-302 specifically targets and binds to CLDN18.2 expressed on tumor cells. Upon internalization and the release of MMAE, MMAE targets and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in CLDN18.2-expressing tumor cells. CLDN18.2, a tight junction protein and stomach-specific isoform of claudin-18, is expressed on a variety of tumor cells. Its expression in healthy tissues is strictly confined to short-lived differentiated epithelial cells of the gastric mucosa. LM-302 是一种抗体药物共轭物（ADC），由针对肿瘤相关抗原（TAA）claudin 18.2（CLDN18.2；claudin-18 的 A2 异构体）的单克隆抗体通过可裂解连接体与具有潜在抗肿瘤活性的微管干扰细胞毒剂单甲基澳瑞他汀 E（MMAE）共轭组成。给药后，抗 CLDN18.2 ADC LM-302 可特异性靶向并结合肿瘤细胞上表达的 CLDN18.2。MMAE 内化并释放后，会与微管蛋白靶向结合，抑制微管聚合。这将导致表达 CLDN18.2 的肿瘤细胞进入 G2/M 期细胞周期并凋亡。CLDN18.2是一种紧密连接蛋白，也是胃特异性的claudin-18异构体，在多种肿瘤细胞中都有表达。它在健康组织中的表达严格限制在胃黏膜的短寿命分化上皮细胞中。2023年10月，LM-302 被NMPA拟纳入突破性治疗，用于治疗既往接受过二线及以上系统治疗的Claudin18.2阳性的局部晚期或转移性胃或胃食管交界处腺癌。 231031 pj D0482 新增药物 SXZ
CMG901 An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against the tumor-associated antigen (TAA) Claudin18.2 (CLDN18.2; A2 isoform of claudin-18) conjugated via a cleavable linker, to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, anti-CLDN18.2 ADC CMG901 specifically targets and binds to CLDN18.2 expressed on tumor cells. Upon internalization and the release of MMAE, MMAE targets and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in CLDN18.2-expressing tumor cells. CLDN18.2, a tight junction protein and stomach-specific isoform of claudin-18, is expressed on a variety of tumor cells. Its expression in healthy tissues is strictly confined to short-lived differentiated epithelial cells of the gastric mucosa. CMG901 是一种抗体药物共轭物（ADC），由针对肿瘤相关抗原（TAA）Claudin18.2（CLDN18.2；Claudin-18 的 A2 异构体）的单克隆抗体通过可裂解连接体与具有潜在抗肿瘤活性的微管干扰细胞毒剂单甲基澳瑞他汀 E（MMAE）共轭组成。给药后，抗 CLDN18.2 ADC CMG901 可特异性靶向并结合肿瘤细胞上表达的 CLDN18.2。内化和释放 MMAE 后，MMAE 靶向并与微管蛋白结合，抑制微管聚合。这将导致表达 CLDN18.2 的肿瘤细胞进入 G2/M 期细胞周期并凋亡。CLDN18.2是一种紧密连接蛋白，也是胃特异性的claudin-18异构体，在多种肿瘤细胞中都有表达。它在健康组织中的表达严格限制在胃黏膜的短寿命分化上皮细胞中。 2022年9月，CMG901 获 CDE 授予突破性治疗药物认定，用于治疗经一线及以上治疗失败或不能耐受的Claudin 18.2阳性晚期胃癌。 231031 pj D0484 新增药物 SXZ
ORIC-114 An orally bioavailable, central nervous system (CNS) penetrating, mutant-selective covalent inhibitor of epidermal growth factor receptor (EGFR; ErbB1) and human epidermal growth factor receptor 2 (HER2; EGFR2; ErbB2) alterations, including exon 20 insertion (Ex20ins) mutations, with potential antineoplastic activity. Upon oral administration, EGFR/HER2 inhibitor ORIC-114 selectively targets, irreversibly binds to and inhibits the activity of EGFR or HER2 insertions or mutations. This prevents EGFR/HER2-mediated signaling. This may induce cell death and inhibit tumor growth in EGFR/HER2-overexpressing tumor cells. ORIC-114 is able to penetrate the blood-brain-barrier (BBB) and may therefore exert its activity against EGFR Ex20ins-driven CNS primary tumors and CNS metastases. The ErbB receptor tyrosine kinase family is involved in key cellular functions, including cell growth and survival. EGFR and HER2 alterations constitutively upregulate kinase activity. ORIC-114 是一种口服生物活性、中枢神经系统（CNS）穿透性、突变选择性共价抑制剂，可抑制表皮生长因子受体（EGFR；ErbB1）和人表皮生长因子受体 2（HER2；EGFR2；ErbB2）的突变，包括外显子 20 插入（Ex20ins）突变，具有潜在的抗肿瘤活性。口服给药后，EGFR/HER2抑制剂 ORIC-114 可选择性地靶向EGFR或HER2插入突变，与之不可逆地结合并抑制其活性。这就阻止了EGFR/HER2介导的信号传导。这可能会诱导细胞死亡，并抑制表达EGFR/HER2的肿瘤细胞的生长。ORIC-114 能够穿透血脑屏障（BBB），因此可对EGFR Ex20ins 驱动的中枢神经系统原发性肿瘤和中枢神经系统转移瘤发挥活性。ErbB受体酪氨酸激酶家族参与了细胞生长和存活等关键细胞功能。表皮生长因子受体（EGFR）和表皮生长因子受体（HER2）的改变会使激酶活性上调。 231101 pj D0486 新增药物 SXZ
Pembrolizumab 帕博利珠单抗 Keytruda 可瑞达 默沙东 2014/9/4 FDA/NMPA KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated: Melanoma ? for the treatment of patients with unresectable or metastatic melanoma. (1.1) ? for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection. (1.1) Non-Small Cell Lung Cancer (NSCLC) ? in combination with pemetrexed and platinum chemotherapy, as first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations. -1.2 ? in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, as first-line treatment of patients with metastatic squamous NSCLC. (1.2) ? as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is: o Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or o metastatic. (1.2, 2.1) ? as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. (1.2, 2.1) ? for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. (1.2) ? as a single agent, for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC. (1.2) Head and Neck Squamous Cell Cancer (HNSCC) ? in combination with platinum and FU for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC. (1.3) ? as a single agent for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test. (1.3, 2.1) ? as a single agent for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. (1.3) Classical Hodgkin Lymphoma (cHL) ? for the treatment of adult patients with relapsed or refractory cHL. (1.4) ? for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy. (1.4) Primary Mediastinal Large B-Cell Lymphoma (PMBCL) ? for the treatment of adult and pediatric patients with refractory PMBCL, or who have relapsed after 2 or more prior lines of therapy. (1.5) ? Limitations of Use: KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy. Urothelial Carcinoma in combination with enfortumab vedotin, for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.1 (1.6) ? as a single agent for the treatment of patients with locally advanced or metastatic urothelial carcinoma who: o are not eligible for any platinum-containing chemotherapy, or o who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum?containing chemotherapy. (1.6) ? as a single agent for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. (1.6) Microsatellite Instability-High or Mismatch Repair Deficient Cancer ? for the treatment of adult and pediatric patients with unresectable or metastatic micros
Ivosidenib 艾伏尼布 Tibsovo 施维雅 43301 FDA TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible IDH1 mutation as detected by an FDA-approved test with: Newly Diagnosed Acute Myeloid Leukemia (AML) In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy (1.1). Relapsed or refractory AML ? For the treatment of adult patients with relapsed or refractory AML (1.2). Relapsed or refractory Myelodysplastic Syndromes (MDS) ? For the treatment of adult patients with relapsed or refractory myelodysplastic syndromes (1.3). Locally Advanced or Metastatic Cholangiocarcinoma ? For the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma who have been previously treated (1.4). TIBSOVO是一种异柠檬酸脱氢酶-1 (IDH1)抑制剂，适用于携带易感性IDH1突变的患者，包括：1. 新诊急性髓系白血病(AML)：与阿扎胞苷联合使用或作为单药用于治疗新近诊断的75岁及以上成人，或因合并症无法使用强化诱导化疗的AML患者。2. 复发或难治性AML：用于治疗复发或难治性AML成人患者。3. 复发或难治性骨髓增生异常综合征(MDS)：用于治疗复发或难治性MDS成人患者。4. 局部晚期或转移性胆管癌：用于治疗既往接受过治疗的局部晚期或转移性胆管癌成人患者。 急性髓系白血病、骨髓增生异常综合征、胆管癌 Ivosidenib is a small molecule inhibitor that targets the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of ivosidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of ivosidenib sustainable at the recommended dosage according to validated methods. The most common of such mutations are R132H and R132C substitutions.Ivosidenib was shown to inhibit selected IDH1 R132 mutants at much lower concentrations than wild-type IDH1 in vitro. Inhibition of the mutant IDH1 enzyme by ivosidenib led to decreased 2- HG levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH1-mutated AML. In blood samples from patients with AML with mutated IDH1, ivosidenib decreased 2-HG levels ex-vivo, reduced blast counts, and increased percentages of mature myeloid cells. Ivosidenib是靶向异柠檬酸脱氢酶1（IDH1）酶突变的小分子抑制剂。IDH1易感突变定义为可导致白血病细胞中2-羟基戊二酸（2-HG）水平升高的突变，其功效可通过以下方法预测：1）依维西尼布推荐剂量下具有临床意义的缓解，和/或2）根据验证方案，在推荐剂量可持续浓度下的依维替尼对IDH1突变酶活性的抑制作用。最常见的此类突变是R132H和R132C替换。Ivosidenib在体外能以比抑制野生型IDH1低得多的浓度选择性抑制IDH1 R132突变。Ivosidenib对突变IDH1酶的抑制在体外试验和IDH1突变AML小鼠异种移植模型中可导致2-HG水平降低，并诱导髓样分化。在IDH1突变AML患者的血液样本中，Ivosidenib可降低离体的2-HG水平，减少原始细胞计数，并增加成熟髓样细胞的百分比。 FDA-Revised:10/2023 45250 pj D0502 新增FDA批准信息 SXZ
PRT543 An orally available small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5), with potential antiproliferative and antineoplastic activities. Although the exact mechanism of action has not been completely determined, upon oral administration, PRMT5 inhibitor PRT543 selectively binds to the substrate recognition site of PRMT5 and inhibits its methyltransferase activity. This decreases the levels of both monomethylated and dimethylated arginine residues in histones H2A, H3 and H4 and modulates the expression of genes involved in several cellular processes, including cellular proliferation. As a result, PRT543 may increase the expression of antiproliferative genes and/or decrease the expression of genes that promote cell proliferation, which may lead to decreased growth of rapidly proliferating cells, including cancer cells. PRTM5, an arginine methyltransferase that catalyzes the formation of both omega-N monomethylarginine (MMA) and symmetric dimethylarginine (sDMA) on histones and a variety of other protein substrates, is overexpressed in several neoplasms. PRT543 是一种可口服的蛋白精氨酸甲基转移酶 5（PRMT5）小分子抑制剂，具有潜在的抗增殖和抗肿瘤活性。虽然确切的作用机制尚未完全确定，但口服 PRMT5 抑制剂 PRT543 可选择性地与 PRMT5 的底物识别位点结合，并抑制其甲基转移酶活性。这将降低组蛋白 H2A、H3 和 H4 中单甲基化和二甲基化精氨酸残基的水平，并调节参与多种细胞过程（包括细胞增殖）的基因的表达。因此，PRT543 可能会增加抗增殖基因的表达和/或减少促进细胞增殖基因的表达，这可能会导致包括癌细胞在内的快速增殖细胞的生长减少。PRTM5 是一种精氨酸甲基转移酶，可催化组蛋白和其他多种蛋白质底物上ω-N 甲基精氨酸（MMA）和对称二甲基精氨酸（sDMA）的形成。 2023/11/20 0:00 pj D0511 新增药物 SXZ
PRT1419 An orally bioavailable inhibitor of the anti-apoptotic protein myeloid cell leukemia 1 (MCL1; induced myeloid leukemia cell differentiation protein; myeloid cell leukemia-1; Mcl-1; Bcl2-L-3), with potential antineoplastic activity. Upon oral administration, the MCL1 inhibitor PRT1419 targets and binds to MCL1. This prevents the binding of MCL1 to and inactivation of certain pro-apoptotic proteins. This promotes apoptosis of cells overexpressing MCL1. MCL1, an anti-apoptotic protein belonging to the Bcl-2 family of proteins, is upregulated in cancer cells and promotes tumor cell survival. PRT1419 是一种抗凋亡蛋白髓系细胞白血病 1（MCL1；诱导髓系白血病细胞分化蛋白；髓样细胞白血病-1；Mcl-1；Bcl2-L-3）的口服生物活性抑制剂，具有潜在的抗肿瘤活性。口服 MCL1 抑制剂 PRT1419 后，会与 MCL1 靶向结合。这可防止 MCL1 与某些促凋亡蛋白结合并使其失活。这将促进过量表达 MCL1 的细胞凋亡。MCL1 是一种属于 Bcl-2 蛋白家族的抗凋亡蛋白，在癌细胞中上调并促进肿瘤细胞的存活。 2023/11/20 0:00 pj D0513 新增药物 SXZ
PRT3789 A targeted protein degrader (TPD) of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2; BRM), with potential antineoplastic activity. PRT3789 is comprised of an E3 ubiquitin ligase-binding moiety conjugated, via a chemical linker, to a SMARCA2-binding moiety. Upon administration of SMARCA2 degrader PRT3789, the SMARCA2-binding moiety specifically targets and binds to SMARCA2 and the E3 ubiquitin ligase-binding moiety targets and binds to the E3 ubiquitin ligase, thereby forming a ternary complex. This induces E3 ligase ubiquitination and proteasome-mediated degradation of SMARCA2. This may lead to the inhibition of the SWI/SNF (BRG1/BRM-associated factor; BAF) chromatin remodeling complex, disrupt chromatin remodeling and gene expression, and result in the downregulation of oncogenic pathways and the inhibition of tumor cell proliferation in SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4; BRG1)-deleted cancers. SMARCA2 and SMARCA4 are the primary ATPase components and mutually exclusive core catalytic subunits of the SWI/SNF chromatin remodeling complex, an important regulator of transcriptional programs and gene expression. SMARCA4 expression is absent in certain cancer cells, and these SMARCA4-deleted cancer cells depend on SMARCA2 for survival. PRT3789 是一种具有潜在抗肿瘤活性的 SWI/SNF 相关基质相关肌动蛋白依赖性染色质亚家族 A 成员 2（SMARCA2；BRM）靶向蛋白降解剂（TPD）。PRT3789 由一个 E3 泛素连接酶结合分子与一个 SMARCA2 结合分子通过化学连接体连接而成。服用 SMARCA2 降解剂 PRT3789 后，SMARCA2 结合分子特异性地靶向并结合 SMARCA2，E3 泛素连接酶结合分子靶向并结合 E3 泛素连接酶，从而形成三元复合物。这将诱导 E3 连接酶泛素化和蛋白酶体介导的 SMARCA2 降解。这可能会导致 SWI/SNF（BRG1/BRM 相关因子；BAF）染色质重塑复合物受到抑制，破坏染色质重塑和基因表达，从而在 SWI/SNF 相关基质相关肌动蛋白依赖性染色质亚家族 A 成员 4（SMARCA4；BRG1）缺失的癌症中下调致癌途径并抑制肿瘤细胞增殖。SMARCA2和SMARCA4是SWI/SNF染色质重塑复合物的主要ATP酶成分和互斥的核心催化亚基，是转录程序和基因表达的重要调节因子。某些癌细胞缺乏 SMARCA4 表达，而这些 SMARCA4 缺失的癌细胞依赖 SMARCA2 存活。 2023/11/20 0:00 pj D0516 新增药物 SXZ
Nirogacestat Ogsiveo SpringWorks 45257 FDA OGSIVEO is a gamma secretase inhibitor indicated for adult patients with progressing desmoid tumors who require systemic treatment. OGSIVEO是一种γ-分泌酶抑制剂，适用于需要系统治疗的侵袭性硬纤维瘤成人患者。 硬纤维瘤 Nirogacestat is a gamma secretase inhibitor that blocks proteolytic activation of the Notch receptor. When dysregulated, Notch can activate pathways that contribute to tumor growth. Nirogacestat是一种γ-分泌酶抑制剂，可阻断Notch受体的蛋白水解激活。当失调时，Notch可激活促进肿瘤生长的信号通路。 FDA-approval:11/2023 45260 pj D0523 新增药物 SXZ
Simmitinib 希美替尼 An orally bioavailable inhibitor of numerous tyrosine kinases (TKs) including fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor type 2 (VEGFR2; KDR), and colony stimulating factor 1 receptor (CSF1R; CSF-1R), with potential antiangiogenic and antineoplastic activities. Upon oral administration, simmitinib binds to and inhibits the activities of these TKs, thereby preventing both the activation of downstream signaling pathways and the proliferation of tumor cells overexpressing these TKs. FGFR, VEGFR2, and CSF1R are upregulated in a variety of cancer cell types and play key roles in tumor cell proliferation, angiogenesis, and metastasis. Simmitinib (SOMCL-15-290) 是一种口服生物活性抑制剂，能抑制多种酪氨酸激酶（TKs），包括成纤维细胞生长因子受体（FGFR）、血管内皮生长因子受体 2 型（VEGFR2；KDR）和集落刺激因子 1 受体（CSF1R；CSF-1R），具有潜在的抗血管生成和抗肿瘤活性。口服后，simmitinib 可与这些 TK 结合并抑制其活性，从而阻止下游信号通路的激活和过表达这些 TK 的肿瘤细胞的增殖。表皮生长因子受体（FGFR）、血管内皮生长因子受体2（VEGFR2）和CSF1R在多种癌细胞类型中上调，并在肿瘤细胞增殖、血管生成和转移中发挥关键作用。 2023/12/1 0:00 pj D0524 新增药物 SXZ
Foscenvivint A potent, specific inhibitor of the canonical Wnt signaling pathway in cancer stem cells with potential antineoplastic activity. Foscenvivint specifically inhibits the recruiting of beta-catenin with its coactivator CBP (the binding protein of the cAMP response element-binding protein CREB); together with other transcription factors beta-catenin/CBP binds to WRE (Wnt-responsive element) and activates transcription of a wide range of target genes of Wnt/beta-catenin signaling. Blocking the interaction of CBP and beta-catenin by this agent prevents gene expression of many proteins necessary for growth, thereby potentially suppressing cancer cell growth. The Wnt/beta-catenin signaling pathway regulates cell morphology, motility, and proliferation; aberrant regulation of this pathway leads to neoplastic proliferation. Foscenvivint (PRI-724) 是癌症干细胞中典型 Wnt 信号通路的强效特异性抑制剂，具有潜在的抗肿瘤活性。Foscenvivint 能特异性地抑制 β-catenin 与其辅助激活因子 CBP（cAMP 反应元件结合蛋白 CREB 的结合蛋白）的结合；β-catenin/CBP 与其他转录因子结合到 WRE（Wnt 反应元件）上，激活 Wnt/β-catenin信号转导的多种靶基因的转录。这种药剂能阻断 CBP 和 β-catenin 的相互作用，阻止许多生长所需的蛋白质的基因表达，从而有可能抑制癌细胞的生长。Wnt/β-catenin 信号通路调节细胞的形态、运动和增殖；该通路的异常调节会导致肿瘤性增殖。 2023/12/1 0:00 pj D0525 新增药物 SXZ
Zongertinib 勃林格殷格翰 非小细胞肺癌 An orally bioavailable inhibitor of the receptor tyrosine kinase human epidermal growth factor receptor 2 (HER2; ErbB2; HER-2), with potential antineoplastic activity. Upon oral administration, HER2 inhibitor BI 1810631 covalently binds to and inhibits the activity of both wild-type and HER2 mutants, including HER2 mutants with exon 20 insertion (ex20ins) mutations. This prevents HER2-mediated signaling and may lead to cell death in HER2-expressing tumor cells. HER2, a receptor tyrosine kinase overexpressed on a variety of tumor cell types, plays an important role in tumor cell proliferation and tumor vascularization. Zongertinib (BI-1810631) 是一种可口服的受体酪氨酸激酶人表皮生长因子受体 2（HER2；ErbB2；HER-2）抑制剂，具有潜在的抗肿瘤活性。口服给药后，HER2 抑制剂 BI 1810631 可与野生型和 HER2 突变体共价结合并抑制其活性，包括具有外显子 20 插入（ex20ins）突变的 HER2 突变。这能阻止 HER2 介导的信号传导，并可能导致表达 HER2 的肿瘤细胞死亡。HER2是一种在多种肿瘤细胞类型中过度表达的受体酪氨酸激酶，在肿瘤细胞增殖和肿瘤血管形成中发挥着重要作用。 BI-1810631是勃林格殷格翰在研的一种新型选择性口服小分子抑制剂，其选择性抑制HER2而不影响野生型EGFR；临床前数据显示其对HER2突变均具有强效的抑制活性，同时可有效避免EGFR相关的剂量限制性毒性。Beamion Lung 1是一项正在进行的Ia/Ib期临床研究，从2023年ASCO公布的Ia期最新数据来看，BI-1810631单药治疗在HER2突变的NSCLC中显示出了非常不错的治疗效果，同时具备较好的安全性数据。 2023/12/4 0:00 pj D0529 更新药物名称 SXZ
Tepotinib 特泊替尼 Tepmetko 拓得康 默克雪兰诺 44230 FDA/NMPA TEPMETKO is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymalepithelial transition (MET) exon 14 skipping alterations. TEPMETKO是一种激酶抑制剂，适用于携带MET 14号外显子跳跃突变的转移性非小细胞肺癌成人患者。2023年12月5日，拓得康（盐酸特泊替尼片）获国家药品监督管理局(NMPA)批准，用于治疗携带间质上皮转化因子（MET）外显子14跳跃突变的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。 非小细胞肺癌 Tepotinib is a kinase inhibitor that targets MET, including variants with exon 14 skipping alterations.Tepotinib inhibits hepatocyte growth factor (HGF)-dependent and -independent MET phosphorylationand MET-dependent downstream signaling pathways. Tepotinib also inhibited melatonin 2 andimidazoline 1 receptors at clinically achievable concentrations.In vitro, tepotinib inhibited tumor cell proliferation, anchorage-independent growth, and migration ofMET-dependent tumor cells. In mice implanted with tumor cell lines with oncogenic activation of MET,including METex14 skipping alterations, tepotinib inhibited tumor growth, led to sustained inhibition ofMET phosphorylation, and, in one model, decreased the formation of metastases. Tepotinib是一种靶向MET（包括14号外显子跳跃突变）的激酶抑制剂。Tepotinib可抑制肝细胞生长因子（HGF）依赖性和非依赖性MET磷酸化以及依赖MET的下游信号通路。Tepotinib还可以在临床可达到的浓度下抑制褪黑素2和咪唑啉1型受体。在体外，Tepotinib可以抑制肿瘤细胞增殖、锚定非依赖性生长和MET依赖性肿瘤细胞的迁移。在植入具有MET致癌活性肿瘤细胞系(包括MET 14号外显子跳跃突变)的小鼠中，Tepotinib抑制了肿瘤的生长，导致MET磷酸化的持续抑制，并且在一个模型中，降低了转移的形成。 FDA-approval:02/2021；NMPA核准日期: 2023年12月5日 45271 pj D0530 更新药物中文名称，NMPA获批信息 SXZ
PLX2853 An orally bioavailable inhibitor of the bromodomain-containing protein 4 (BRD4), with potential antineoplastic activity. Upon oral administration, the BRD4 inhibitor PLX2853 binds to the acetylated lysine recognition motifs in the bromodomains of the BRD4 protein, thereby preventing the binding of BRD4 to acetylated lysines on histones. This disrupts chromatin remodeling and dyregulates gene expression. This may lead to the downregulation of the expression of certain growth-promoting genes, which may induce apoptosis and inhibit the proliferation of BRD4-overexpressing tumor cells. BRD4, a member of the human bromodomain and extra-terminal (BET) family of proteins, is a transcriptional regulator that is overexpressed in certain tumor cells and plays an important role in cellular proliferation. PLX2853 是一种口服生物可用的含溴结构域蛋白 4 (BRD4) 抑制剂，具有潜在的抗肿瘤活性。口服后，BRD4 抑制剂 PLX2853 会与 BRD4 蛋白溴结构域中的乙酰化赖氨酸识别基团结合，从而阻止 BRD4 与组蛋白上的乙酰化赖氨酸结合。这就破坏了染色质重塑并导致基因表达失调。这可能会导致某些促进生长的基因表达下调，从而诱导凋亡并抑制过量表达 BRD4 的肿瘤细胞的增殖。BRD4是人类溴域和末端外（BET）蛋白家族的成员，是一种转录调节因子，在某些肿瘤细胞中过度表达，在细胞增殖中发挥重要作用。 2023/12/18 0:00 pj D0534 新增药物 SXZ
JIN-A02 J INTS BIO 非小细胞肺癌 JIN-A02 is a novel, orally available, fourth-generation EGFR tyrosine kinase inhibitor (TKI) targeting C797S mutation and has demonstrated potent anti-tumor activity in preclinical models of double- or triple-mutant EGFR (ex19del/T790M or ex19del/T790M/C797S) (Abstract MA07.08). JIN-A02是一种新型、可口服的靶向 C797S 突变的第四代 EGFR 抑制剂(TKI) ，并且已经在双或三突变 EGFR (ex19del/T790M 或 ex19del/T790M/C797S)的临床前模型中显示出有效的抗肿瘤活性。 JIN-A02是一种新型、口服靶向C797S突变的第四代EGFR TKI。临床前研究中，JIN-A02在EGFR双突变或三突变（19外显子缺失/T790M突变，或19外显子缺失/T790M突变/C797S突变）患者中显示出较好的抗肿瘤活性。 230713 pj D0537 新增药物 LXL
LS-106 复旦大学 非小细胞肺癌 Taken together, we identified LS-106 as a novel fourth-generation EGFR inhibitor against C797S mutation and confirmed its preclinical antitumor effects in C797S-triple-mutant tumor models (PMID: 34855271). LS-106是一种针对C797S突变的第四代新型EGFR抑制剂，并在C797S三突变肿瘤模型中证实了其临床前抗肿瘤效果。 LS-106是由我国研究者发现报道的一种四代EGFR-TKI。在无细胞系统中LS-106可抑制EGFR-Del19/T790M/C797S、EGFR-L858R/T790M/C797S、EGFR-L858R/T790M和野生型EGFR，细胞实验和动物实验也证实了其对EGFR-Del19/T790M/C797S 的抑制能力。 230713 pj D0538 新增药物 LXL
Axitinib 阿昔替尼 Inlyta 英立达 辉瑞 40935 FDA/NMPA INLYTA is a kinase inhibitor indicated: in combination with avelumab, for the first-line treatment of patients with advanced renal cell carcinoma (RCC). in combination with pembrolizumab, for the first-line treatment of patients with advanced RCC. as a single agent, for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. INLYTA是一种激酶抑制剂，适应症包括：1.与阿维鲁单抗联合用于晚期肾细胞癌（RCC）患者的一线治疗。2.与帕博利珠单抗联用，用于晚期RCC患者的一线治疗。3.作为单药，用于治疗既往接受过一次系统治疗失败后的晚期肾细胞癌（RCC）。2014年，NMPA批准阿昔替尼用于既往接受过一种酪氨酸激酶抑制剂或细胞因子治疗失败的进展期肾细胞癌（RCC）的成人患者。 肾细胞癌 Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGF-mediated endothelial cell proliferation and survival were inhibited by axitinib in vitro and in mouse models. Axitinib was shown to inhibit tumor growth and phosphorylation of VEGFR-2 in tumor xenograft mouse models. 阿昔替尼在治疗血浆浓度下可抑制受体酪氨酸激酶，包括血管内皮生长因子受体（VEGFR）-1、VEGFR-2和VEGFR-3。这些受体与病理性血管生成、肿瘤生长和癌症进展有关。阿昔替尼在体外和小鼠模型中抑制VEGF介导的内皮细胞增殖和存活。在肿瘤异种移植小鼠模型中，阿昔替尼可抑制肿瘤生长和VEGFR-2的磷酸化。 09/2022 230718 pj D0547 新增药物 LXL
SC-10914 迪诺医药/青峰医药 实体瘤 SC10914 is a highly potent PARP inhibitor (PARP1 IC50 = 7.87 nM) with potent anti-proliferative activity against human BRCA deficient tumor cells (MDA-MB-436, BRCA1 deficient, IC50 = 4.03 nM, Capan-1 BRCA2 deficient, IC50 = 11.66 nM) and PTEN deficient tumor cells (HGC-27,PTEN deficient, IC50 = 0.35 μM). SC10914 showed potent anti-tumor activity in BRCA1/2 mutant tumor models and better pharmacokinetics profile has the potential to be selected as the clinical candidate for the treatment of treatment of BRCA1/2 deficient cancers. SC10914是一种高效 PARP 抑制剂(PARP1 IC50 = 7.87 nM) ，具有针对人 BRCA 缺陷型肿瘤细胞(MDA-MB-436，BRCA1缺陷型，IC50 = 4.03 nM，Capan-1 BRCA2缺陷型，IC50 = 11.66 nM)和 PTEN 缺陷型肿瘤细胞(HGC-27，PTEN 缺陷型，IC50 = 0.35 μM)的有效抗增殖活性。SC10914在 BRCA1/2突变肿瘤模型中显示出有效的抗肿瘤活性，更好的药代动力学特征有可能被选为治疗 BRCA1/2缺陷型癌症的临床候选药物。 SC-10914，由上海迪诺医药科技和青峰医药集团研发，目前在中国处于临床I期，用于治疗ATM阴性或BRCA1或BRCA2突变的晚期恶性肿瘤、经3线或更多线化疗后、携带有害或疑似有害种系BRCA突变的晚期卵巢癌的单药治疗、铂敏感的、BRCA突变的（种系和/或体细胞）复发性高分化浆液性上皮卵巢癌、输卵管癌或原发性腹膜癌的单药维持疗。2015年6月，申报中国化药1.1类临床研究（化药1类），并于2016年8月获得临床试验批件。2016年9月，评价SC10914在晚期实体肿瘤患者中的安全性、耐受性，药代动力学/药效动力学及初步疗效的I期临床研究（CTR20160752、NCT02940132、QF-SC10914-011）在中国开始。 230718 pj D0548 新增药物 LXL
Tisotumab vedotin-tftv Tivdak Seagen 2021/9/20 FDA TIVDAK is a tissue factor-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK是一种组织因子靶向抗体和微管抑制剂偶联物，用于治疗化疗期间或之后疾病进展的复发性或转移性宫颈癌成人患者。 宫颈癌 Tisotumab vedotin-tftv is a tissue factor (TF)-directed antibody drug conjugate (ADC). The antibody is a human IgG1 directed against cell surface TF. TF is the primary initiator of the extrinsic blood coagulation cascade. The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease-cleavable linker. Nonclinical data suggests that the anticancer activity of tisotumab vedotin-tftv is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin-tftv also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. Tisotumab vedotin-tftv是一种组织因子（TF）导向的抗体药物偶联物（ADC）。该抗体是一种针对细胞表面TF的人源IgG1。TF是外源性血液凝固级联的主要启动因子。小分子MMAE是一种微管破坏剂，通过蛋白酶可切除连接体连接到抗体上。非临床数据表明，tisotumab vedotin-tftv的抗癌活性是由于ADC与表达TF的癌细胞结合，随后ADC-TF复合物内化，并通过蛋白酶裂解释放MMAE。MMAE破坏活跃分裂细胞的微管网络，导致细胞周期停滞和细胞凋亡。在体外，tisotumab vedotin-tftv还能介导抗体依赖性细胞吞噬和抗体依赖性细胞毒性。 09/2021 230718 pj D0552 新增药物 LXL
9MW2821 迈威生物 实体瘤 An antibody drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the cell surface adhesion molecule and tumor-associated antigen (TAA) nectin-4 (PVRL4), site-specifically conjugated, via a linker, to the cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration of the anti-nectin-4 ADC 9MW2821, the anti-nectin-4 antibody targets and binds to nectin-4 expressed on tumor cells. Upon binding and internalization, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces apoptosis in nectin-4-expressing tumor cells. Nectin-4, a TAA belonging to the nectin family, is overexpressed in a variety of cancers, but has a restricted distribution in normal tissue. 9MW2821 是一种抗体药物共轭物（ADC），由一种针对细胞表面粘附分子和肿瘤相关抗原（TAA）脊髓灰质炎病毒受体4（Nectin-4；PVRL4）的人源化单克隆抗体，通过连接子与细胞毒剂单甲基澳瑞他汀 E（MMAE）定点共轭组成，具有潜在的抗肿瘤活性。服用 9MW2821 后，抗 nectin-4 抗体会靶向并结合肿瘤细胞上表达的 nectin-4。结合和内化后，MMAE 会与微管蛋白结合并抑制其聚合，从而导致 G2/M 期停滞并诱导表达 nectin-4 的肿瘤细胞凋亡。Nectin-4 是一种属于Nectin家族的TAA，在多种癌症中过度表达，但在正常组织中分布有限。 迈威生物的9MW2821是基于ADC药物开发平台和自动化高通量杂交瘤抗体分子发现平台开发的一款靶向Nectin-4的ADC新药。9MW2821结构均一、容易产业化，体外药效活性、体内代谢性质、初步安全性等方面均显示其良好的成药性，在多种动物肿瘤模型中均具有良好的抗肿瘤效果，下一步的临床试验将会揭示其临床价值。 230810 pj D0562 新增药物 LXL
