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 赫赛汀 罗氏制药 2013/2/22 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 2023/6/2 sxz D0003
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 Rybrevant 杨森生物 2021/5/21 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 2021/11/26 D0009
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0.5-0.8?nM，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
AZD5363|Capivasertib 乳腺癌 Capivasertib has been investigated for the treatment of Metastatic Breast Cancer. capivasertib临床研究的适应症为：capivasertib联合氟维司群对比安慰剂联合氟维司群，治疗芳香酶抑制剂治疗期间或治疗后复发或进展的局部晚期（不可手术）或转移性激素受体阳性、人表皮生长因子受体2 阴性(HR+/HER2-) 乳腺癌。 2021/11/26 D0017
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). 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）。 2021/11/26 D0019
BAY-86-9766|Refametinib 瑞美替尼 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] 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] 2021/11/26 D0020
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 Helsinn?Healthcare 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 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. 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。 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。 01/2019 2021/11/26 D0026
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 Takeda?Pharms?USA 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。 2021/11/26 D0029
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。 2021/11/26 D0039
Crizotinib 克唑替尼 Xalkori 赛可瑞 PF?Prism?CV 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 Pfizer?Europe?MA?EEIG 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
Debio-1347|CH5183284 Ch5183284 has been used in trials studying the treatment of Solid Tumours. Ch5183284已用于研究治疗固体瘤的试验中。 2021/11/26 D0044
Fam-trastuzumab deruxtecan-nxki 德曲妥珠单抗 Enhertu 优赫得 Daiichi Sankyo Europe GmbH 2019/12/20 0:00 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。023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。 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 2023/5/26 0:00 sxz D0045 批准单位更新 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
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|GDC-0068 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是一种高度选择性的口服ATP竞争性小分子AKT抑制剂.在细胞系和异种移植模型中，ipatasertib在多种癌症类型，包括前列腺癌，乳腺癌，卵巢癌，结肠直肠癌和非小细胞肺癌中都表现出了抗癌活性。 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）。 230627 pj D0063 药物信息补充 SXZ
Inavolisib|GDC-0077 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（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。 44526 D0064 补充英文名称
GDC-0980|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。 2021/11/26 D0065
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。 2021/11/26 D0068
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 Waldenstr?m’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）。 2021/11/26 D0083
Neratinib 奈拉替尼 Nerlynx 贺俪安 Puma Biotechnology, Inc 2017/7/17 0:00 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。 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 230711 pj D0085 药物机制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<E8BE85>
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>
OTX015|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））。 2021/11/26 D0091
Palbociclib 哌柏西利 Ibrance 爱博新 Pfizer?Europe?MA?EEIG 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. 培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。 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。 08/2022 2023/5/26 0:00 sxz D0097 商品名修改 LXL
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 Takeda?Pharms?USA 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 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批准瑞派替尼适用晚期胃肠道间质瘤(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）。瑞普替尼（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）。瑞普替尼（Ripretinib）在体外可抑制其他激酶，如PDGFRB、BRAF、VEGF和TIE2基因（PubMed: 31205499，PubMed: 31267077）。瑞普替尼（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”。瑞普替尼（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 2023/6/20 sxz D0109
RO5045337 RO-5045337 is under investigation in clinical trial NCT01164033 (A Study of RO5045337 in Patients With Solid Tumors). RO-5045337正在进行临床试验NCT01164033（RO5045337对实体瘤患者的研究）。 2021/11/26 D0110
Rucaparib 芦卡帕尼 Rubraca Clovis Oncology, Inc 2016/12/19 FDA RUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:1.Ovarian cancer (1)for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. (2)for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. 2.Prostate cancer for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (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：(1)用于对铂类化疗完全或部分反应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。(2)既往接受过两种或两种以上化疗且携带有害BRCA突变(胚系和/或体细胞)相关卵巢上皮癌、输卵管癌或原发性腹膜癌成人患者。2.既往接受过雄激素受体导向疗法和紫杉烷为基础化疗且携带有害BRCA突变(胚系和/或体细胞)相关转移性去势抵抗性前列腺癌(mCRPC)。 卵巢癌、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。 09/2021 2021/11/26 D0112
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 43389 FDA TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. TALZENNA是一种聚（ADP核糖）聚合酶（PARP）抑制剂，适用于携带有害或可疑有害胚系BRCA突变(gBRCAm)、HER2阴性的局部晚期或转移性乳腺癌成人患者，或联合恩扎卢胺用于HRR基因（ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C）突变的转移性去势抵抗性前列腺癌成人患者。 乳腺癌、前列腺癌 Talazoparib binds to and inhibits PARP1 and PARP2 at the NAD+ binding site with a Ki of 1.2 and 0.87 nM, respectively(PubMed:26652717). The inhibitory effect on PAR synthesis has an EC50 of 2.51 nM. 他拉唑帕尼（Talazoparib）与NAD+结合位点结合并抑制PARP1和PARP2，Ki值分别为1.2和0.87 nM（PubMed: 26652717）。对PAR合成的抑制作用的EC50值为2.51 nM。 06/2023 230625 pj D0122 新增适应症 SXZ
Taselisib Taselisib has been used in trials studying the treatment and basic science of LYMPHOMA, Breast Cancer, Ovarian Cancer, Solid Neoplasm, and HER2/Neu Negative, among others. Taselisib已用于研究淋巴瘤、乳腺癌、卵巢癌、实体瘤和HER2/Neu阴性等的治疗和基础科学的试验中。Taselisib是一种PI3K抑制剂，设计用于结合PI3Kα的ATP结合口袋来阻止传递下游信号，从而阻止PI3Kα突变细胞系的生长. 2021/11/26 D0123
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 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). 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）。 2021/11/26 D0127
TK216 2021/11/26 D0128
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-na?ve 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>
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正处于晚期胃腺癌治疗的研究中。 2021/11/26 D0136
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 Margenza Macrogenics Inc 2020/12/16 FDA 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。 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 2021/11/26 pj/sjz D0140
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.Waldenstr?m’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 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。 2022/1/24 sxz D0165
GI-4000 SAR125844, 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突变的重组面包酵母的疫苗，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。 2022/1/24 sxz D0166
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 1905/7/13 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，适用于肾细胞癌（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）成年患者。 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。 08/2021 2022/2/14 sxz D0176
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 2020/4/22 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 20230601 pj D0190 新增药物；批准单位更新 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 NCI Thesaurus
Tovorafenib 胶质瘤 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。 230606 pj D0240 新增药物 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
Enfortumab Vedotin 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 230625 pj D0298 药物新增 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
Navitoclax 艾伯维 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损伤时--例如来自辐射的损伤--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。 44590 sxz D0347 PJ
Mirvetuximab soravtansine-gynx Elahere ImmunoGen 44879 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 230710 pj D0349 药物新增 lxl lxl
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 lxl
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 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 (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。<E4BD93><E38082>
