database/target_drug.txt

药物名称-英文	药物名称-中文	商品名-英文	商品名中文	公司	上市年份	批准单位	适应症（英文）	适应症（中文）	适应症（癌种）	作用机制-英文	作用机制-中文	药物说明书版本	研究现状	编辑时间	编辑人	ID	备注（内容，日期，备注者）	审核人
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	
Almonertinib	阿美替尼	Almonertinib Mesilate Tablets	阿美乐	豪森药业	2020/3/17	NMPA		甲磺酸阿美替尼是表皮生长因子受体（EGFR）的激酶抑制剂，适用于既往经表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI)治疗时或治疗后出现疾病进展，并且经检测确认存在EGFR T790M 突变阳性的局部晚期或转移性非小细胞肺癌成人患者的治疗;适用于治疗表皮生长因子受体（EGFR）19号外显子缺失或21号外显子L858R置换突变的局部晚期或转移性非小细胞肺癌成人患者的一线治疗。	非小细胞肺癌		甲磺酸阿美替尼是表皮生长因子受体（EGFR）的激酶抑制剂，对 EGFR 耐药或激活突变（T790M、L858R 和 Del19）产生不可逆抑制的 IC50 较野生型低约 10 倍。在体外细胞增殖和体内动物肿瘤移植瘤模`型中，甲磺酸阿美替尼对携带 EGFR 突变（T790M/L858R 和 Del19）的非小细胞肺癌细胞株具有抗肿瘤作用，对野生型 EGFR 抑制作用较弱。	03/2020		2021/11/26		D0006		
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		
AMG-337										AMG 337可有效地抑制野生型MET以及在乳头状细胞癌中的MET突变体的酶活，同时可抑制PC3细胞中HGF所诱导的MET磷酸化。AMG 337 抑制MET依赖性癌细胞的增殖，在MET信号放大的胃癌细胞中通过PI3K和MAPK信号通路对细胞增殖和生存发挥作用，在24小时连续施药，完全抑制MET的情况下，其耐受性良好。			AMG-337正处于临床试验NCT03147976中QUILT-3.036：AMG 337用于治疗晚期或转移性实体瘤受试者。因而，AMG 337具有在人类癌症中检验MET作用的临床属性。	2021/11/26		D0008		
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		
Anlotinib	安罗替尼		福可维	正大天晴	2018/5/8	NMPA		安罗替尼是一种多靶点的受体酪氨酸激酶(RTK)抑制剂。其适应症包括：1.用于既往至少接受过2种系统化疗后出现进展或复发的局部晚期或转移性非小细胞肺癌患者的治疗。对于存在表皮生长因子受体(EGFR)基因突变或间变性淋巴瘤激酶(ALK)阳性的患者,在开始本品治疗前应接受相应的标准靶向药物治疗后进展、且至少接受过2种系统化疗后出现进展或复发。2.用于腺泡状软组织肉瘤、透明细胞肉瘤以及既往至少接受过含蒽环类化疗方案治疗后进展或复发的其他晚期软组织肉瘤患者的治疗。3.用于既往至少接受过2种化疗方案治疗后进展或复发的小细胞肺癌患者的治疗。4.用于具有临床症状或明确疾病进展的、不可切除的局部晚期或转移性甲状腺髓样癌患者的治疗。国家卫健委《新型抗肿瘤药物临床应用指导原则（2020年版）》指出安罗替尼适用于晚期肾细胞癌(RCC)中高危患者的一线治疗和曾接受VEGFR-TKI治疗失败的晚期RCC患者的治疗。	非小细胞肺癌，小细胞肺癌，软组织肉瘤，甲状腺髓样癌，肾细胞癌	盐酸安罗替尼（AL3818，Anlotinib Hydrochloride）是一种新型小分子多靶点酪氨酸激酶抑制剂，能有效抑制VEGFR、PDGFR、FGFR、c-Kit等激酶，具有抗肿瘤血管生成和抑制肿瘤生长的作用。该药是正大天晴药业集团自主研发的抗肿瘤1.1类新药，目前多种癌症临床试验正在开展当中，包括非小细胞肺癌、软组织肉瘤、胃癌、结直肠癌、甲状腺髓样癌、分化型甲状腺癌以及食管鳞癌。	安罗替尼是一种多靶点的受体酪氨酸激酶(RTK)抑制剂。激酶抑制试验结果显示，安罗替尼可抑制VEGFR1 (IC50为26.9 nM)、VEGFR2 (IC50为0.2 nM) 、VEGFR3 (IC50为0.7 nM) 、c-Kit (IC50为14.8 nM) 、PDGFRβ (IC50为115 nM)的激酶活性。体外试验结果显示，安罗替尼可抑制多种肿瘤细胞株(786-O、A375、A549、Caki-1、U87MG、MDA-MB-231、HT-29、NCI-H526、HMC-1)的增殖，IC50 3.0-12.5 uM之间；在HUVECs细胞中可显著抑制VEGFR2的磷酸化水平及下游相关蛋白的磷酸化，在Mo7e细胞中可显著抑制c-Kit的磷酸化水平及下游相关蛋白的磷酸化，在U87MG细胞中可显著抑制PDGFR的磷酸化水平及下游相关蛋白的磷酸化；可显著抑制VEGF-A刺激下的HUVECs的增殖、迁移、小管形成；可抑制大鼠动脉环微血管样结构的形成。	02/2021		2021/11/26	pj/sjz	D0010		
Apatinib	阿帕替尼		艾坦	恒瑞医药	2019/9/30	NMPA		阿帕替尼为一种小分子血管内皮细胞生长因子受体 2（VEGFR-2） 酪氨酸激酶抑制剂，适应症包括：1.单药用于既往至少接受过 2 种系统化疗后进展或复发的晚期胃腺癌或胃-食管结合部腺癌患者。患者接受治疗时应一般状况良好。2.单药用于既往接受过至少一线系统性治疗后失败或不可耐受的晚期肝细胞癌患者。	胃癌、食管胃交界处腺癌、肝细胞癌		甲磺酸阿帕替尼为一种小分子血管内皮细胞生长因子受体 2（VEGFR-2） 酪氨酸激酶抑制剂，可抑制肿瘤血管生成。动物研究表明甲磺酸阿帕替尼对多种小鼠肿瘤模型的肿瘤生长具有抑制作用。	03/2020	艾坦（阿帕替尼）是全球第一个在晚期胃癌被证实安全有效的小分子抗血管生成靶向药物，也是晚期胃癌标准化疗失败后，明显延长生存期的单药。同时，该药是胃癌靶向药物中唯一一个口服制剂，可有效提高患者治疗的依从性，并明显降低治疗费用。高度选择性竞争细胞内VEGFR-2的ATP结合位点，阻断下游信号转导，抑制肿瘤组织新血管生成。2014年12月13日，中国自主研制的用于治疗晚期胃癌的小分子靶向药物“甲磺酸阿帕替尼片”获得国家食品药品监管局批准上市。用于治疗既往至少接受过2种系统化疗后进展或复发的晚期胃腺癌或胃食管结合部腺癌患者，且患者接受阿帕替尼治疗时一般状况良好。	2021/11/26	pj/sjz	D0011		
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		
AZD4547				阿斯利康、和誉医药							AZD4547是一款强效、高选择性的口服小分子FGFR1-3抑制剂。在临床前研究中，AZD4547在相关肿瘤模型中单药效果显著。相应的临床研究也显示出其良好的安全耐受性，并在FGFR基因异常的肿瘤患者中展现出明显的药效。		AZD4547用于非小细胞肺癌、乳腺癌、胃癌等治疗的临床试验中。	2023/4/25	pj	D0016		sxz
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		
Belvarafenib				基因泰克					黑素瘤		Belvarafenib (GDC5573, HM95573, RG6185)是一种选择性的、具有生物口服利用度的pan-RAF kinase抑制剂，对WT BRAF、BRAF（V600E）、CRAF激酶的IC50值分别为41 nM、7 nM和2 nM。HM95573对突变型BRAF和CRAF激酶具有高选择性，它对WT BRAF、BRAF(V600E)、CRAF的IC50值分别为41 nM、7 nM和2 nM。除此之外，HM95573还抑制CSF1R、DDR1、DDR2，IC50分别为44 nM、77 nM和182 nM。HM95573可有效地抑制含突变型BRAF的黑素瘤细胞株如A375（IC50: 57 nM）和SK-MEL-28 (IC50：69 nM)，以及含突变型NRAS的黑素瘤细胞株如SK-MEL-2（IC50: 53 nM）和SK-MEL-30 (IC50：24 nM)。在这些细胞中，HM95573还抑制了与细胞增殖相关的MEK和ERK下游激酶的磷酸化。在移植有突变BRAF(e.g. A375和SK-MEL-28)和突变NRAS（e.g. SK-MEL-2和SK-MEL-30)细胞系的小鼠移植瘤模型中，HM95573具有良好的抗肿瘤活性。		Belvarafenib可有效地抑制含突变型BRAF的黑素瘤细胞株如A375（IC50: 57 nM）和SK-MEL-28 (IC50：69 nM)，以及含突变型NRAS的黑素瘤细胞株如SK-MEL-2（IC50: 53 nM）和SK-MEL-30 (IC50：24 nM)。在这些细胞中，Belvarafenib还抑制了与细胞增殖相关的MEK和ERK下游激酶的磷酸化。在移植有突变BRAF(e.g. A375和SK-MEL-28)和突变NRAS（e.g. SK-MEL-2和SK-MEL-30)细胞系的小鼠移植瘤模型中，HM95573具有良好的抗肿瘤活性。	2021/11/26		D0021		
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		2023-05-10 00:00:00	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		
Curaxin|CBL0137									乳腺癌		CBL0137 (Curaxin-137)是一种 histone chaperone FACT (facilitates chromatin transcription) 的抑制剂，可同时抑制 NF-κB 并激活 p53，对应的EC50值分别为0.47 μM和0.37 μM。		curaxin可用来治疗雌激素受体阳性(ER+)和/或人表皮生长因子受体2阳性(HER2)和/或孕酮受体阳性(PR)和/或促染色质转录阳性(FACT+)的乳腺癌。	230602	pj	D0032	名称修订	LXL
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
Chidamide	西达本胺	Epidaza	爱谱沙	微芯生物	2014/12/23	NMPA		西达本胺为苯酰胺类组蛋白去乙酰化酶（Histone Deacetylase，HDAC）亚型选择性抑制剂，适应症包括：1.用于既往至少接受过一次全身化疗的复发或难治的外周 T 细胞淋巴瘤（PTCL）患者。2.联合芳香化酶抑制剂用于激素受体阳性、人表皮生长因子受体-2 阴性、绝经后、经内分泌治疗复发或进展的局部晚期或转移性乳腺癌患者。	淋巴瘤，乳腺癌		本品为苯酰胺类组蛋白去乙酰化酶（Histone Deacetylase，HDAC）亚型选择性抑制剂，主要针对第 I 类 HDAC 中的 1、2、3 亚型和第 IIb 类的 10 亚型，具有对肿瘤异常表观遗传功能的^调控作用。西达本胺通过抑制相关 HDAC 亚型以增加染色质组蛋白的乙酰化水平来引发染色质重塑，并由此产生针对多条信号传递通路基因表达的改变（即表观遗传改变），进而抑制肿瘤细胞周期、诱导肿瘤细胞凋亡，同时对机体细胞免疫具有整体调节活性，诱导和增强自然杀伤细胞（NK）和抗原特异性细胞毒 T 细胞（CTL）介导的肿瘤杀伤作用。西达本胺还通过表观遗传调控机制，具有诱导肿瘤干细胞分化、逆转肿瘤细胞的上-皮间充质表型转化（EMT）等功能，进而在恢复耐药肿瘤细胞对药物的敏感性和抑制肿瘤转移、复发等方面发挥潜在作用。	1/2015	西达本胺于2014年12月23日获NMPA批准上市，适用于既往至少接受过一次全身化疗的复发或难治的外周T细胞淋巴瘤（PTCL）患者。2019年11月29月，深圳微芯生物科技股份有限公司自主研发的全新分子体、国际上首个口服剂型亚型选择性组蛋白去乙酰化酶（HDAC）抑制剂、国家1.1类新药西达本胺（Chidamide，商品名：爱谱沙/ Epidaza?）新适应症 -- 联合芳香化酶抑制剂用于治疗激素受体阳性、人表皮生长因子受体-2阴性、绝经后、经内分泌治疗复发或进展的局部晚期或转移性乳腺癌患者 -- 获得国家药品监督管理局（NMPA）正式批准，这是西达本胺继复发及难治性外周T细胞淋巴瘤之后在中国获批的第二个适应症。西达本胺是组蛋白去乙酰化酶（HDAC）抑制剂，对特定HDAC亚型的抑制及由此产生的染色质重构与基因转录调控作用（即表观遗传调控作用），抑制淋巴及血液肿瘤的细胞周期并诱导肿瘤细胞凋亡；诱导和增强自然杀伤细胞（NK）和抗原特异性细胞毒T细胞（CTL）介导的肿瘤杀伤作用及抑制肿瘤病理组织的炎症反应，不仅能直接贡献于对T淋巴瘤中循环肿瘤细胞及局部病灶产生疗效作用，同时也可能应用于诱导和增强针对其他类型肿瘤的抗肿瘤细胞免疫的整体调节活性。	2021/11/26	pj/sjz	D0036		
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.	2017-09-14 00:00:00	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		2023-05-26 00:00:00	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	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)胶质瘤患者 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 tumor cell lines in vitro
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 00:00:00	FDA/NMPA	ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of: 1.adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either: in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy. 2.adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. 3.adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.4.adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.	ENHERTU是一种HER2靶向抗体和拓扑异构酶抑制剂偶联物，其适应症为：1.携带HER2阳性，前期已接受过以抗HER2为基础的治疗(转移性疾病治疗或新辅助/辅助治疗）并在完成治疗期间或6个月内出现疾病复发的不可切除性或转移性乳腺癌成人患者。2.患者ERBB2低表达(IHC 1+或IHC 2+/ISH-)且在疾病转移后接受过化疗或在完成辅助化疗期间或6个月内发生疾病复发的不可切除或转移性成年乳腺癌患者。3.携带HER2 (ERBB2)激活突变的不可切除或转移性非小细胞肺癌(NSCLC)成人患者。4.既往接受过基于曲妥珠单抗治疗的HER2阳性、局部进展或转移性胃或胃食管交界处腺癌的成人患者。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		2023-05-26 00:00:00	sxz	D0045	批准单位更新	LXL
Disitamab	纬迪西妥单抗		爱地希	荣昌生物	2021/6/8	NMPA		维迪西妥单抗是一种抗体药物偶联剂,适用于至少接受过 2 个系统化疗的 HER2 过表达局部晚期或转移性胃癌(包括胃食管结合部腺癌)的患者。	胃癌、胃食管交界处腺癌		爱地希（纬迪西妥单抗）注射剂，Disitamab Vedotin?（研发代号：RC48）是中国第1个提交新药上市申请的自主开发的抗体-药物偶联物（ADC）。ADC由单克隆抗体、连接子和小分子细胞毒药物偶联而成。纬迪西妥单抗以肿瘤表面的HER2蛋白为靶点，能精准识别癌细胞并与之结合，穿透细胞膜进入其内部，从而杀死癌细胞。	07/2021		2021/11/26	pj/sjz	D0046		
Donafenib	多纳非尼			泽璟制药	2021/6/8	NMPA		多纳非尼是一种多激酶抑制剂，适用于既往未接受过全身系统性治疗的不可切除肝细胞癌患者，也同样适用于局部晚期/转移性放射性碘难治性分化型甲状腺癌患者的治疗。	肝癌		甲苯磺酸多纳非尼为索拉非尼的氘代化合物，理论上其作用机制与索拉非尼相同，为多激酶抑制剂。甲苯磺酸多纳非尼在体外可抑制多种人肿瘤细胞的增殖，在多种人源肿瘤(包括肾癌、肝癌、乳腺癌和结直肠癌)的裸小鼠移植性肿瘤模型中可抑制肿瘤生长。在多种新生血管生成评价模型中，甲苯磺酸多纳非尼可抑制新生血管生成。	06/2021	甲苯磺酸多纳非尼片（Donafenib）是由中国自主研发的靶向药，是一种新型的多激酶抑制剂。药理研究表明，多纳非尼可以同时抑制VEGFR、PDGFR等多种受体酪氨酸激酶的活性，也可直接抑制各种Raf激酶，并抑制下游的Raf/MEK/ERK信号传导通路，抑制肿瘤细胞增殖和肿瘤血管的形成，发挥双重抑制、多靶点阻断的抗肿瘤作用。?ZGDH3研究是中国首个完成的、用于评估多纳非尼一线治疗晚期肝细胞癌的II/III期的临床试验，从2016年3月至2018年4月共招募了668位患者，是迄今为止中国患者入组数最多的一线晚期肝癌临床试验。在今年刚结束的56届美国肿瘤学会年会（ASCO2020）上，研究者通过口头报告向全世界公布了ZGDH3最新研究成果，证明了多纳非尼在肝癌靶向治疗方面取得突破性进展。2020年7月3日，中国临床肿瘤学会（CSCO）正式公布新版的《原发性肝癌诊疗指南》。在这次指南更新中，中国本土制药企业苏州泽璟生物制药股份有限公司自主研发的创新药——多纳非尼已被列为晚期肝细胞癌（HCC）一线治疗药物，并且是I级专家推荐和1A类证据。这是继索拉非尼和仑伐替尼之后，第一个而且是唯一一个列入CSCO指南的囯产一线治疗肝癌的分子靶向药物，对我国乃至全球肝癌的治疗，都具有划时代的重大科学意义和实用价值！（图1指南）??原发性肝癌在我国高发常见，位居第四位恶性肿瘤，而死亡人数仅次于肺癌；据统计每年约有 46.6万新发病例，42.2万病死，均超过了全球的一半，严重威胁人民生命和健康。“中国原发性肝癌登记调查研究项目（CLCS)”表明：我国的HCC与欧美国家明显不同，具有高度的异质性，乙型肝炎病毒感染相关HCC的比例较高，且80%的HCC患者在初诊时已达中晚期，失去根冶机会；同时大多数患者合并有基础肝病（肝炎和肝硬化），肝功能较差，导致治疗困难，治疗效果差，患者的生存期很短。因此，我国的肝癌诊疗绝对不能完全照搬国外的经验，本土大样本临床研究及其数据至关重要。????继2007年欧美批准索拉非尼用于一线治疗HCC之后的10年间， 全球学者陆续开展了一系列针对晚期HCC的一线治疗药物的大型临床研究，但是无不以失败告终。直至2018年，才有第二个一线靶向治疗药物仑伐替尼，通过非劣于索拉非尼的总生存期的研究获批上市。???????据悉，本次CSCO《原发性肝癌诊疗指南》更新之所以将多纳非尼纳入且鼎力推荐，正是基于近期在ASCO年会期间公布的多纳非尼与索拉非尼头对头比较一线治疗晚期HCC的多中心ll/lll期临床研究（ZGDH3试验）的优良结果。该研究由著名肿瘤专家秦叔逵和毕锋教授等独立设计和组织实施，共纳入668例中国HCC患者，是迄今为止针对中国人样本量最大的肝癌临床研究。值得强调的是，ZGDH3试验与REFLECT、CheckMate459 以及IMBrave150研究相比，入组患者的基线状态更差、病情更复杂，包括HBV病因占比较高、BCLC C期及Child-Pugh B级比例较高等，贴近我国晚期HCC患者的实际状态，更符合国情。?
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		
EAI045											EAI045是一种靶向特定耐药性的EGFR突变体的变构抑制剂。对野生型受体无作用。EAI045有效抑制H1975细胞中EGFR(Y1173)的磷酸化（EC50=2 nM），但在具有野生EGFR的HaCaT细胞（角质形成细胞系）中无此效果。尽管EAI045对EGFR的突变体有抑制作用，但在H1975和H3255细胞中，尽管浓度达到了10 μM，EAI也没有抗增殖作用。EAI045 能够抑制EGFR（L858R和T790M）突变体，IC50为3 nM。然而，它不能够完全阻止具有EGFR（L858R/T790M）突变体的H1975细胞中EGFR的自身磷酸化。二聚作用有缺陷的/独立的突变体对EAI045更敏感。因为EGFR的激酶激活需要形成二聚体，EAI045可能对EGFR异聚体的某一个亚基具有抑制活性。在小鼠中进行的药代动力学研究表明EAI045的最大血浆浓度为0.57 μM，其半衰期为2.15小时。在给药浓度为20 mg/kg的情况下，其生物利用率为26%。当EAI045与另一阻止EGFR二聚的化合物cetuximab结合使用时，在具有EGFR（L858R/T790M）突变体驱动下的肺癌小鼠模型中，EAI045能显著的减少肿瘤生长。单独EAI045给药的小鼠则没有治疗效果。EAI045与cetuximab结合使用还能在具有L858R/T790M/C797S突变的小鼠中诱导肿瘤体积缩小。说明EAI045和cetuximab具有协同作用。			2021/11/26		D0049		
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		
Endostatin	重组人血管内皮抑制素		恩度	先声药业	2006/8/18	NMPA		Endostatin是一种血管生成抑制类新生物制品，其适应症为联合长春瑞滨/顺铂(NP)化疗方案用于治疗初治或复治的Ⅲ/Ⅳ期非小细胞肺癌(NSCLC)患者。	非小细胞肺癌		重组人血管内皮抑制素为血管生成抑制类新生物制品，其作用机理是通过抑制形成血管的内皮细胞迁移来达到抑制肿瘤新生血管的生成，阻断了肿瘤细胞的营养供给，从而达到抑制肿瘤增殖或转移目的。体外实验结果显示，本品对人微血管内皮细胞株 HHEC 的迁移、Tube 形成有抑制作用，并能明显抑制鸡胚尿囊膜血管生成，提示本品具有一定的体外抗血管生成作用。此外，本品对人肺腺癌细胞 SPC-A4 有一定的生长抑制作用。体内实验结果显示，本品对鼠肿瘤模型 (S180肉瘤、H22肝癌)，人异种移植肿瘤 (SPG-A4 肺腺癌、SGC7901胃癌、Hela 宫颈癌、SMMC-7721 和 Bel7402肝癌)有抑瘤作用。	03/2011	恩度（重组人血管内皮抑制素注射液），是我国科学家在内皮抑素的基础上外加了9个氨基酸，研究开发出的拥有民族自主知识产权的1.1类抗肿瘤血管靶向药物。2005年9月恩度被NMPA(原SFDA)批准联合长春瑞滨/顺铂用于中国晚期非小细胞肺癌（NSCLC）患者的治疗。目前恩度抗血管生成联合化疗已经成为中国晚期非小细胞肺癌一线治疗的标准方案。	2021/11/26	pj/sjz	D0052		
Ensartinib	恩沙替尼		贝美纳	贝达药业	2020/11/17	NMPA		恩沙替尼为间变性淋巴瘤激酶（ALK）抑制剂，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		恩沙替尼为间变性淋巴瘤激酶（ALK）抑制剂，对ALK的半数抑制浓度（IC50）小于 0.25 nM，对 Ephrin A2 激酶（EPHA2）、MET 受体酪氨酸激酶（c-MET）亦可见抑制作用。恩沙替尼可抑制 HEK-293 细胞（过表达 EML4-ALK E13;A20）ALK 自磷酸化，也可抑制非小细胞肺癌细胞 H3122（EML4-ALK E13;A20）ALK磷酸化，同时抑制相应下游信号分子 AKT、ERK 及 mTOR 底物-核糖体蛋白（S6）的磷酸化。恩沙替尼对非小细胞肺癌细胞 H3122、H2228，淋巴瘤细胞 SUDHL-1 以及神经母细胞瘤细胞 SH-SY5Y 的 IC50 分别为 0.015 μM、0.045 μM、0.009 μM 和0.068 μM；对 c-MET 扩增的胃腺癌细胞 MKN-45 抑制作用的 IC50 为 0.156 μM；对转染了克唑替尼耐药突变体 EML4-ALK L1196M 或 C1156Y 的 Ba/F3 细胞抑制作用的 IC50 分别 0.106 μM 和 0.048 μM。	11/2020	恩莎替尼（Ensartinib，X-396）是贝达药业和其控股子公司Xcovery共同开发的第二代ALK抑制剂。贝达药业今年已向中国药审中心申请盐酸恩莎替尼胶囊上市，用于治疗此前接受过克唑替尼治疗后进展的或者对克唑替尼不耐受的ALK阳性的局部晚期或转移性NSCLC患者。?2020年11月19日，贝达药业股份有限公司发布公告，公司收到国家药监局（NMPA）核准签发的《药品注册证书》（药品批准文号：国药准字H20200009、国药准字H20200010），盐酸恩沙替尼胶囊（商品名：贝美纳?）正式获批上市，成为中国第一个用于治疗ALK突变晚期非小细胞肺癌的国产1类新药。盐酸恩沙替尼是一种新型强效、高选择性的新一代ALK抑制剂，是贝达药业和控股子公司Xcovery共同开发的全新的、拥有完全自主知识产权的创新药。2018年12月，恩沙替尼用于接受过克唑替尼治疗后进展的或者对克唑替尼不耐受的ALK阳性的局部晚期或转移性非小细胞肺癌患者的药品注册申请获得国家药监局受理。2019年2月，恩沙替尼被国家药监局药品审评中心(CDE)纳入优先审评品种名单。此后，相继完成国家药监局食品药品审核查验中心（CFDI）组织开展的临床核查和注册现场检查。?盐酸恩沙替尼国内Ⅱ期注册临床研究由中山大学肿瘤防治中心张力教授牵头，共有27家国内医学中心参与。研究结果于2019年10月在国际著名医学学术期刊《柳叶刀?呼吸医学》（The Lancet Respiratory Medicine）全文发表。随后更新的数据显示，恩沙替尼治疗克唑替尼耐药患者的整体ORR为52.6%，疾病控制率为87.8%，中位PFS为11.2个月，颅内ORR为71.4%，颅内疾病控制率为95.2%。研究证明，恩沙替尼在疗效上与同类进口药相比更有优势，特别是在颅内转移的患者中有更高的应答率，并具有良好可控的安全性。	2022/4/12	sxz	D0053		
Entrectinib	恩曲替尼	Rozlytrek	罗圣全	Roche Pharma (Schweiz) AG	2019-08-15 00:00:00	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		2023-05-26 00:00:00	sxz	D0054	批准单位更新	LXL
Erdafitinib	厄达替尼	Balversa		杨森生物	2019/4/12	FDA	BALVERSA is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has susceptible FGFR3 or FGFR2 genetic alterations and progressed during or following at least one line of prior platinumcontaining chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.	BALVERSA是一种激酶抑制剂，适用于既往接受至少一种含铂化疗期间（新辅助或辅助含铂化疗的12个月内）或之后疾病进展的携带FGFR3或FGFR2易感遗传变异的局部晚期或转移性尿路上皮癌成人患者。	尿路上皮癌	Urothelial cancer is statistically the fourth most common kind of cancer in the world. In general, such urothelial cancers originate in the urothelium - or the transitional epithelium - a membrane that covers the renal pelvis to the ureter, the bladder, and the proximal two-thirds of the urethra. While 90 to 95% of urothelial cancers are bladder cancers and the other 5 to 10% are upper tract urothelial cancers, the bladder cancers can also be either superficial or invasive (either not having or having invaded the deeper layers of the bladder).Moreover, fibroblast growth factor receptor (FGFR) is a transmembrane protein that is expressed ubiquitously in normal tissues and is involved in various endogenous bio-physiological processes including the homeostasis of phosphate and vitamin D, cell proliferation, cell anti-apoptotic signaling, and cell migration in a variety of cell types(PubMed:28965185). Concurrently, genetic mutations or changes like deregulation of FGFR pathways and FGFR aberrations such as gene amplification, point mutations, and chromosomal translocations have been implicated in the pathogenesis of urothelial cancer, including the possibility of such changes to all four FGFR genes (FGFR1, FGFR2, FGFR3, and FGFR4)(PubMed:28965185). Changes to the FGFR genes are consequently thought to promote cell proliferation, migration, angiogenesis, and anti-apoptosis in many cancers including urothelial cancer(PubMed:28965185).Erdafitinib is subsequently an oral selective pan-FGFR kinase inhibitor that binds to and inhibits the enzymatic activity of expressed FGFR1, FGFR2, FGFR3, and FGFR4 based on in vitro data(PubMed:28965185,PubMed:26324363). In particular, erdafitinib demonstrates inhibition of FGFR phosphorylation and signaling as well as decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions(PubMed:28965185,PubMed:26324363). Erdafitinib demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer(PubMed:28965185,PubMed:26324363).	统计数据显示，尿路上皮癌已成为全球第四大常见肿瘤。通常而言，尿路上皮癌起源于尿道上皮（或称移行上皮，一种覆盖肾盂至输尿管、膀胱和尿道近端三分之二的膜）。90-95%的尿路上皮癌是膀胱癌，而其他5-10%是上尿路上皮癌，膀胱癌根据是否侵入膀胱深层可分为浅表性或浸润性膀胱癌。此外，成纤维细胞生长因子受体（FGFR）是一种跨膜蛋白，在正常组织中广泛表达，并参与各种内源性生理进程，包括磷酸盐和维生素D稳态，多种细胞类型的增殖、抗凋亡信号和迁移（PubMed: 28965185）。同时，包括FGFR通路失控和FGFR畸变（如基因扩增、点突变和染色体易位）在内的基因突变或遗传变异，都与尿路上皮癌的发病机理有关，这种变异在所有四个FGFR基因（FGFR1、FGFR2、FGFR3和FGFR4）上都有可能发生（PubMed: 28965185）。因此，FGFR基因变异被认为可促进多种肿瘤（包括尿路上皮癌）细胞的增殖、迁移，血管生成和抗凋亡（PubMed: 28965185）。厄达替尼（Erdafitinib）是一种口服选择性泛FGFR激酶抑制剂，基于体外试验数据，该抑制剂与表达的FGFR1、FGFR2、FGFR3和FGFR4结合<E7BB93>
Erlotinib	厄洛替尼	Tarceva	特罗凯	罗氏制药	2004/11/18	FDA/NMPA	TARCEVA is a kinase inhibitor indicated for: 1.The treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test receiving first-line, maintenance, or second or greater line treatment after progression following at least one prior chemotherapy regimen. 2.First-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer, in combination with gemcitabine.	TARCEVA是一种激酶抑制剂，其适应症为：1.在至少一种化疗方案失败后接受一线、维持第二线或更多线治疗的表皮生长因子受体(EGFR)19号外显子缺失或21号外显子L858R置换突变的转移性非小细胞肺癌(NSCLC)。2.联合吉西他滨用于局部晚期、不可切除性或转移性胰腺癌的一线治疗。2006年厄洛替尼得到NMPA首次批准，2017年NMPA批准厄洛替尼单药适用于表皮生长因子受体（EGFR）基因具有敏感突变的局部晚期或转移性非小细胞肺癌（NSCLC）患者的治疗，包括一线治疗、维持治疗，或既往接受过至少一次化疗进展后的二线及以上治疗。	非小细胞肺癌、胰腺癌	Epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells. In some tumor cells signaling through this receptor plays a role in tumor cell survival and proliferation irrespective of EGFR mutation status. Erlotinib reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor and thereby inhibiting further downstream signaling. Erlotinib binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higher than its affinity for the wild type receptor. Erlotinib inhibition of other tyrosine kinase receptors has not been fully characterized.	表皮生长因子受体（EGFR）在正常细胞和肿瘤细胞表面都有表达。 在一些肿瘤细胞中，通过该受体的信号传导在肿瘤细胞存活和增殖中均起作用，而与EGFR突变状态无关。厄洛替尼（Erlotinib）可逆地抑制EGFR的激酶活性，阻止受体酪氨酸残基的自磷酸化，进而抑制下游信号传导。厄洛替尼（Erlotinib）对19号外显子缺失或21号外显子（L858R）突变EGFR的结合亲和力高于野生型受体。厄洛替尼（Erlotinib）对其他酪氨酸激酶受体的抑制作用尚未完全表征。	FDA-approval:10/2016;NMPA-approval:?2017		2023/6/20	sxz	D0056	修改日期；220223；sxz	
Everolimus	依维莫司	Afinitor	飞尼妥	诺华制药	2009/3/30	FDA/NMPA	AFINITOR is a kinase inhibitor indicated for the treatment of: 1.Postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole. 2.Adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. 3.Adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. 4.Adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.5.AFINITOR and AFINITOR DISPERZ are kinase inhibitors indicated for the treatment of adult and pediatric patients aged 1 year and older with TSC who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.6.AFINITOR DISPERZ is a kinase inhibitor indicated for the adjunctive treatment of adult and pediatric patients aged 2 years and older with TSC-associated partial-onset seizures.	AFINITOR是一种激酶抑制剂，其适应症为：1.联合依西美坦用于治疗来曲唑或阿那曲唑治疗失败的绝经后妇女激素受体阳性、HER2阴性的晚期乳腺癌。2.进展性胰腺神经内分泌瘤(PNET)以及不可切除性、局部晚期或转移性的进展性、分化良好的非功能性胃肠道(GI)和肺部神经内分泌瘤(NET)成人患者。3.舒尼替尼或索拉非尼治疗失败的晚期肾细胞癌(RCC)成人患者。4.不需要立即手术的肾血管平滑肌脂肪瘤伴结节性硬化症(TSC)成人患者。5.AFINITOR和AFINITOR DISPERZ作为激酶抑制剂，适用于伴有室管膜下巨细胞星形细胞瘤(SEGA)、需要治疗干预但不可手术切除的TSC成人和儿童(≥1岁)患者。6.AFINITOR DISPERZ是一种激酶抑制剂，用于辅助治疗TSC相关癫痫部分性发作的成人和儿童(≥2岁)患者。2013年依维莫司首次获得NMPA批准，2018年NMPA批准依维莫司适用于治疗以下患者：晚期肾细胞癌成人患者，胰腺神经内分泌瘤成人患者.胃肠道或肺源神经内分泌肿瘤（NET）成人患者，室管膜下巨细胞星形细胞瘤(SEGA)，肾血管平滑肌脂肪瘤伴结节性硬化症。2022年NMPA批准依维莫司用于治疗乳腺癌。	乳腺癌、神经内分泌瘤、肾癌、结节性硬化症、巨细胞星形细胞瘤	Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers and in tuberous sclerosis complex (TSC). Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex 1 (mTORC1) and thus inhibition of mTOR kinase activity. Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic initiation factor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis. S6K1 is a substrate of mTORC1 and phosphorylates the activation domain 1 of the estrogen receptor which results in ligand-independent activation of the receptor. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) and reduced the expression of vascular endothelial growth factor (VEGF).Inhibition of mTOR by everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies.Constitutive activation of the PI3K/Akt/mTOR pathway can contribute to endocrine resistance in breast cancer. In vitro studies show that estrogen-dependent and HER2+ breast cancer cells are sensitive to the inhibitory effects of everolimus, and that combination treatment with everolimus and Akt, HER2, or aromatase inhibitors enhances the anti-tumor activity of everolimus in a synergistic manner.Two regulators of mTORC1 signaling
Fedratinib		Inrebic		英派药业	2019/8/16	FDA	INREBIC is a kinase inhibitor indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).	INREBIC是一种激酶抑制剂，适用于治疗中危2型或高危原发性或继发性(真性红细胞增多症或原发性血小板增多症后)骨髓纤维化(MF)成人患者。	骨髓纤维化	Fedratinib is an inhibitor of Janus Activated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3(PubMed:26181658).JAK2 is highly active in myeloproliferative neoplasms like myelofibrosis.Fedratinib's inhibition of JAK2 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and 5, which prevents cell division and induces apoptosis(PubMed:24165976).	Fedratinib是Janus激酶2(JAK2)和FMS样酪氨酸激酶3的抑制剂(PubMed：26181658)。JAK2在诸如骨髓纤维化的骨髓增殖性肿瘤中高度激活。Fedratinib对JAK2的抑制作用会抑制信号转导子和转录激活子(STAT)3和5的磷酸化，阻止细胞分裂并诱导凋亡(PubMed：24165976)。	08/2019		2021/11/26		D0058		
Fruquintinib	呋喹替尼	Elunate	爱优特	和记黄埔	2018/9/4	NMPA		呋喹替尼是具有高度选择性的肿瘤血管生成抑制剂，适用于既往接受过氟尿嘧啶类、奥沙利铂和伊立替康为基础的化疗，以及既往接受过或不适合接受抗血管内皮生长因子(VEGF)治疗、抗表皮生长因子受体(EGFR)治疗(RAS野生型)的转移性结直肠癌(mCRC)患者。	结直肠癌		呋喹替尼是一具有高度选择性的肿瘤血管生成抑制剂，其主要作用靶点是VEGFR激酶家族VEGFR1， 2及3。呋喹替尼在分子水平可抑制VEGFR激酶的活性；在细胞水平上可抑制VEGFR2/3的磷酸化，抑制内皮细胞的增殖及管腔形成；在组织水平上，呋喹替尼可明显抑制鸡胚绒毛尿囊膜模型新生微血管的形成；在整体动物水平上，呋喹替尼口服后可抑制VEGFR2/3磷酸化，抑制肿瘤血管生成，从而抑制肿瘤生长。在整体动物上，呋喹替尼采用一日一次给药，对结直肠癌以及其它多种类型肿瘤模型的生长均显示强效且剂量依赖性的抑制效应，在敏感模型上发现肿瘤缩小和消退。	05/2019		2021/11/26		D0059		
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
Furmonertinib	伏美替尼		艾弗沙	艾力斯	2021/3/2	NMPA		伏美替尼是第3代表皮生长因子受体酪氨酸激酶抑制剂，适用于既往经表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI)治疗时或治疗后出现疾病进展，并且经检测确认存在EGFR T790M突变阳性的局部晚期或转移性非小细胞性肺癌(NSCLC)成人患者的治疗和具有表皮生长因子受体（EGFR）外显子19缺失突变（19DEL）或外显子21置换突变（21L858R）的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者的一线治疗。	非小细胞肺癌		本品属于第三代表皮生长因子受体(EGFR) 酪氨酸激酶抑制剂(TK)。本品具有三氟乙氧基吡啶为基础的结构，无论是药物原型AST2818还是主要代谢产物AST5902，均可通过不饱和丙烯酰胺键与EGFR不可逆结合，具有双活性，可以强效抑制EGFR敏感突变和耐药突变。同时，三氟乙氧基吡啶结构可以阻断非选择性代谢产物的产“生，药物分子具备的空间位阻效应也能提高激酶谱选择性，降低脱靶效应，提高安全性。该品种上市为非小细胞性肺癌(NSCLC)成人患者提供了新的治疗选择。	03/2021		2022/7/11	sxz	D0061		
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	
GDC-0068|Ipatasertib										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已用于研究癌症、肿瘤、实体癌、乳腺癌和胃癌等治疗的试验中。Ipatasertib可靶向并结合AKT（即蛋白激酶B）的所有三种亚型，这三种亚型可以阻断PI3K/AKT信号传导通路，该通路是前列腺癌癌细胞生长和增殖的关键驱动因子。	2021/11/26		D0063		
GDC-0077										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).			GDC-0077正在进行临床试验NCT03006172（评价GDC-0077单药在实体瘤患者以及联合内分泌治疗+靶向治疗在乳腺癌患者中的安全性、耐受性和药代动力学）。	2021/11/26		D0064		
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	
Icotinib	埃克替尼		凯美纳	贝达药业	2011/6/7	NMPA		埃克替尼是一种酪氨酸激酶抑制剂，适用于治疗表皮生长因子受体(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)患者的一线治疗。本品单药可试用于治疗既往接受过至少一个化疗方案失败后的局部晚期或转移性非小细胞肺癌(NSCLC)，既往化疗主要是指以铂类为基础的联合化疗。	非小细胞肺癌		埃克替尼是一种选择性表皮生长因子受体(EGFR)酪氨酸激酶抑制剂。埃克替尼抑制EGFR酪氨酸激酶活性的半数有效浓度(IC50)为5 nM，在所测试的88种激酶中，500 nM浓度的埃克替尼只对EGFR野生型及其突变型有明显的抑制作用，对其它激酶均没有抑制作用，提示埃克替尼是一个高选择性的EGFR激酶抑制剂。体外研究和动物实验表明埃克替尼可抑制多种人肿瘤细胞株的增殖。	10/2014		2021/11/26		D0071		
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
Inetetamab	伊尼妥单抗		赛普汀	三生国健	2020/6/17	NMPA		伊尼妥单抗是一种重组抗人表皮生长因子受体-2 人源化单克隆抗体，适用于与长春瑞滨联合治疗已接受过 1 个或多个化疗方案的HER2 阳性的转移性乳腺癌患者。	乳腺癌		伊尼妥单抗是一种重/组人源化单克隆抗体，特异作用于人表皮生长因子受体-2 (HER2) 的细胞外部位。并且伊尼妥单抗可介导抗体依赖的细胞介导的细胞毒反应（ADCC）。伊尼妥单抗在体外及动物试验中均显示可抑制 HER2 阳性肿瘤细胞的增殖。HER2原癌基因或C-erbB2编码一个单一的受体样跨膜蛋白，分子量为185 kDa，其结构上与其他表皮生长因子受体类似。在原发性乳腺癌患者中观察到有 25%~30% 的患者 HER2 阳性。HER2 基因扩增可导致肿瘤细胞表面 HER2 蛋白表达增加，导致 HER2 蛋白活化。	06/2020	6月19日，三生制药宣布旗下三生国健自主研发的注射用伊尼妥单抗（商品名：赛普汀?）正式获得国家药品监督管理局（NMPA）批准，适用于HER2阳性，与长春瑞滨联合治疗已接受过1个或多个化疗方案的转移性乳腺癌患者。这是中国自主研发上市的首个创新抗HER2单抗药物。Fc段修饰，实现更强ADCC效应与曲妥珠单抗相比，伊尼妥单抗具有相同的2个Fab段，各214个氨基酸，但是对Fc段进行了氨基酸修饰，同时进行了生产工艺优化。因此伊尼妥单抗与曲妥珠单抗的氨基酸序列不完全相同，并不是曲妥珠单抗单抗的生物类似药，而是中国自主研发并首个上市的创新抗HER2单抗。经Fc段修饰后的伊尼妥单抗具有了更强的ADCC（抗体依赖的细胞介导的细胞毒性作用）效应。ADCC是单抗类药物治疗肿瘤的重要机制。从结构上看，单抗类药物的Fab段可特异性结合肿瘤细胞表面抗原；而其Fc段可与NK等细胞的Fcγ受体（FcγR）结合以刺激这些细胞释放多种效应因子杀伤肿瘤细胞，该过程即为ADCC效应。体外研究显示，伊尼妥单抗与曲妥珠单抗具有同样的HRE2抗原的结合活性和亲和力，在对体外癌细胞增殖抑制活性，蛋白空间折叠和热稳定性等几个关键质量属性上两者保持一致。该研究同时显示，伊尼妥单抗的ADCC效应比曲妥珠单抗提高大约11.1%[1]。2019年美国ASCO会议公布了一项抗HER2单抗（Margetuximab）的SOPHIA研究结果。Margetuximab同样是在对Fc段改构后具有了更强的ADCC效应。SOPHIA研究显示，该单抗的治疗与含曲妥珠单抗的治疗相比，可降低转移性乳腺癌患者24%的疾病进展风险[2]；该单抗改构后更强的ADCC效应一定程度上转化为患者的生存获益。伊尼妥单抗作为中国首个Fc段修饰，生产工艺优化，具有更强ADCC效应的创新抗HER2单抗，可以为更多中国HER2阳性癌症患者带来临床获益。伊尼妥单抗将为中国HER2+乳腺癌患者带来治疗新选择研究表明，多种实体肿瘤均有HER2高表达的可能，特别是对于全球女性肿瘤发病率排名第一的乳腺癌，HER2阳性率更是达到20%左右。我国国家癌症中心2019年发布的报告显示，2015年中国乳腺癌新发患者数为30.4万人[3]，其中20%～25%的乳腺癌患者为HER2阳性患者[4] 。HER2阳性的乳腺癌的临床实践尚有巨大的治疗需求未得到满足，患者面临着复发和耐药等多重问题。抗HER2单抗作为IgG1抗体，可参与免疫系统的体液免疫和细胞免疫，以其定向性、高特异性、安全性和低风险，成为HER2阳性乳腺癌、消化道肿瘤等实体瘤的有效治疗手段。上世纪末，中国科学家开启抗体类药物研究的探索之路。中国肿瘤学领域奠基人孙燕院士指导团队开展伊尼妥单抗的一系列临床研究。现任中国临床肿瘤学会乳腺癌专委会主任委员的江泽飞教授领导的团队，历时四年，完成了伊尼妥单抗RCT、多中心、前瞻性Ⅲ<E680A7><E285A2>
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
LOXO-292										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 primarily achieved through chromosomal rearrangements producing 5' fusions of dimerizable domains to the 3'RETtyrosine kinase domain, such asKIF5B-RETandCCDC6-RET, resulting in constitutive dimerization and subsequent autophosphorylation(PubMed:32083997,PubMed:32296961,PubMed:25047660).Constitutive activation leads to increased downstream signalling and is associated with tumour invasion, migration, and proliferation(PubMed:31715421).Selpercatinib is a direct RET kinase inhibitor, exhibiting IC50values between 0.92 and 67.8 nM depending on the exactRETgenotype.Information based on natural as well as induced resistance mutations and molecular modelling suggests that selpercatinib directly inhibits RET autophosphorylation by competing with ATP for binding. Various single amino acid mutations at position 810 inhibit selpercatinib binding without significantly altering ATP binding, potentially leading to treatment failures(PubMed:31988000).Selpercatinib is also reported to inhibit other tyrosine kinase receptors, including VEGFR1, VEGFR3, FGFR1, FGFR2, and FGFR3, at clinically relevant concentrations. The significance of these effects is not well studied.	转染期间重排(RET)激酶是一种跨膜受体酪氨酸激酶，包含完整的胞外、跨膜和胞内结构域，其活性是肾脏和神经系统正常发育所必需的(PubMed:2992805,PubMed:32083997)。RET组成性激活主要由染色体重排所导致，该重排可导致二聚结构域的5'端与RET酪氨酸激酶结构域3'端产生融合（如KIF5B-RET和CCDC6-RET），从而导致组成性的二聚化和随后的自磷酸化(PubMed:32083997,PubMed:32296961,PubMed:25047660)。RET的组成性激活会导致下游信号转导增加，并与肿瘤的侵袭、迁移和增殖有关(PubMed:31715421)。Selpercatinib是一种RET激酶抑制剂，根据确切的RET基因型其IC50值在0.92至67.8 nM之间。基于天然以及诱导的抗性突变和分子模型的信息表明，Selpercatinib通过和ATP竞争结合来直接抑制RET自磷酸化。810位氨基酸上的各种突变可能抑制Selpercatinib的结合能力而不会显著改变ATP的结合能力，进而导致治疗失败（PubMed：31988000）。Selpercatinib在临床相关浓度下还可以抑制其他酪氨酸激酶受体，包括VEGFR1、VEGFR3、FGFR1、FGFR2和FGFR3。这些效果的显著性尚未得到很好的研究。			2021/11/26		D0080		
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		
MK2206											MK-2206 2HCl是一种高度选择性的Akt1/2/3抑制剂，在无细胞试验中IC50分别为8 nM/12 nM/65 nM；对250种其他蛋白激酶没有抑制活性。MK-2206 2HCl 在肿瘤细胞中可诱导自噬和凋亡。Phase 2。MK-2206是变构抑制剂，由pleckstrin同源结构域激活。MK-2206抑制Akt的苏氨酸308位点和丝氨酸473位点的自身磷酸化作用。另外，MK-2206阻止Akt调节的下游信号分子（包括TSC2, PRAS40，及核糖体S6蛋白）的磷酸化作用。与抑制Ras 突变型细胞系(如NCI-H358, NCI-H23, NCI-H1299, 和Calu-6)相比，MK-2206 更有效地抑制Ras野生型细胞系(如A431, HCC827, 和NCI-H292)。MK-2206和细胞毒素药剂如erlotinib 和lapatinib联用作用于肺部NCI-H460肿瘤细胞或者卵巢A2780肿瘤细胞，MK-2206也显示出协同效应。MK-2206和这些细胞毒素药剂联用作用于NCI-H292移植瘤，MK-2206显示出非常有效的抗癌活性。卵巢癌A2780移植瘤中，按动物体重，每千克处理240mg MK-2206,则可抑制70%以上的Akt1/2在苏氨酸308位点和丝氨酸473位点的磷酸化，导致肿瘤生长抑制率达到60%。			2021/11/26		D0084		
Neratinib	奈拉替尼	Nerlynx	贺俪安	Puma Biotechnology, Inc	2017/7/17	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.	来那替尼（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，来那替尼（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。来那替尼（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，口服来那替尼（Neratinib）可以抑制肿瘤生长。	06/2021		2021/11/26		D0085		
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 1.Ovarian cancer .(1)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. (2).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/orgenomic instability.(3).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.(2.Breast cancer:(1)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.(2)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.3.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.4.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. .	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)用于对一线铂类化疗完全或部分反应的携带有害或可疑有害的胚系或体细胞BRCA突变的晚期卵巢上皮癌、输卵管癌或原发性腹膜癌成人患者的维持治疗。(2)联合贝伐单抗用于对一线铂类化疗完全或部分反应，且其癌症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。(3)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.乳腺癌：（1）作为携带有害或可疑有害gBRCAm、HER2阴性且已接受过新辅助、辅助化疗的高危早期乳腺癌成人患者的辅助治疗。（2）用于治疗在新辅助、辅助或转移治疗中接受过化疗的携带有害或可疑有害gBRCAm、HER2阴性转移性乳腺癌成人患者，且激素受体(HR)阳性乳腺癌患者应既往接受过内分泌治疗或认为不适合内分泌治疗。3.用于治疗至少在一线铂化疗方案16周内未进展的携带有害或可疑有害gBRCAm转移性胰腺癌成人患者。4.用于治疗既往接受过恩扎鲁胺或阿比特龙<E789B9>
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
Pamiparib	帕米帕利		百汇泽	百济神州	2021/4/30	NMPA		帕米帕利是一种强效选择性多聚ADP核糖聚合酶(PARP酶，包括PARP1和PARP2)抑制剂，适用于既往经过二线及以上化疗的伴有胚系BRCA(gBRCA)突变的复发性晚期卵巢癌、输卵管癌或原发性腹膜癌患者的治疗。	卵巢癌、输卵管癌或原发性腹膜癌		帕米帕利是一种强效选择性多聚ADP核糖聚合酶(PARP酶，包括PARP1和PARP2)抑制剂，参与DNA修复。体外研究显示，帕米帕利能抑制PARP酶活性以及增加PARP-DNA复合物形成，诱发DNA损伤和癌细胞死亡。帕米帕利可在体外抑制肿瘤细胞的增殖，在小鼠体内抑制人源异种移植肿瘤模型的生长。并且在携带乳腺癌易感基因(BRCA)突变或其他同源重组缺陷(HRD)的肿瘤细胞或小鼠模型中，帕米帕利显示出更强的细胞增殖抑制活性和抗肿瘤作用。	04/2021		2021/11/26		D0093		
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.	2020-04-17 00:00:00	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		2023-05-26 00:00:00	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
PLX8394										PLX8394 is under investigation in clinical trial NCT02428712 (A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors).			PLX8394正在进行临床试验NCT02428712（PLX8394单药治疗晚期无法切除的实体瘤患者研究）。	2021/11/26		D0100		
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>
Pyrotinib	吡咯替尼		艾瑞妮	恒瑞医药	2018/8/12	NMPA		吡咯替尼为小分子受体酪氨酸激酶抑制剂，其适应症为：1.联合卡培他滨治疗表皮生长因子受体 2 (HER2)阳性、既往未接受或接受过曲妥珠单抗的复发或转移性乳腺癌患者，使用本品前患者应接受过蒽环类或紫杉类化疗。2.联合曲妥珠单抗及多西他赛，适用于治疗表皮生长因子受体2（HER2）阳性早期或局部晚期乳腺癌患者的新辅助治疗。3.马来酸吡咯替尼片与曲妥珠单抗和多西他赛联合，用于治疗表皮生长因子受体2（HER2）阳性、晚期阶段未接受过抗HER2治疗的复发或转移性乳腺癌患者。	乳腺癌		吡咯替尼是不可逆的小分子受体酪氨酸激酶抑制剂，显著抑制表皮生长因子受体（ErbB1/EGFR）和人表皮生长因子受体 2（ErbB2/HER2），半数抑制浓度（IC50）分别为 5.6 nM、8.1 nM。吡咯替尼可显著抑制 HER2 高表达的肿瘤细胞（乳腺癌、卵巢癌、胃癌肿瘤细胞）生长，IC50 为 1~43 nM。在多种移植瘤裸小鼠模型（乳腺癌、卵巢癌、肺癌）中，吡咯替尼可显著抑制 HER2 因子驱动的肿瘤生长，抑制 HER2 介导的下游信号通路，将肿瘤细胞阻滞在细胞周期 G1 期。	06/2020	吡咯替尼于2018年08月16日获NMPA（原NMPA）批准上市，联合卡培他滨，适用于治疗表皮生长因子受体2（HER2）阳性、既往未接受或接受过曲妥珠单抗的复发或转移性乳腺癌患者。使用本品前患者应接受过蒽环类或紫杉类化疗。吡咯替尼是一种不可逆的酪氨酸激酶受体抑制剂，包括表皮生长因子受体(EGFR)和表皮生长因子受体2 (HER2)，通过将受体的胞内区ATP酶结合域的半胱氨酸残基烷基化，使受体永久失活。	2023/4/6	sxz	D0104	适应证修改	pj
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	2014-04-21 00:00:00	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		2023-05-26 00:00:00	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		
TPX-0005|Ropotrectinib|Repotrectinib	洛普替尼										Repotrectinib (TPX-0005) 是一种新型的ALK/ROS1/TRK抑制剂，对WT ALK、ALK(G1202R)、ALK(L1196M)的IC50分别为1.01 nM、1.26 nM、1.08 nM；同时也是一种有效的SRC抑制剂，IC50为5.3 nM。TPX-0005是一种具有口服活性的ATP竞争性抑制剂，抑制ALK、ROS1、TRKA、TRKB和TRKC重组激酶以及其相应的临床耐药突变体。在许多人类癌细胞系和工程类稳定表达致癌基因或其突变体的细胞系中，亚纳摩尔或第浓度的纳摩尔级别的TPX-0005能有效发挥其抗增殖活性，伴随着对靶标磷酸化的抑制和使其下游效应分子如ERK、AKT和STAT3失活。TPX-0005在伤口愈合实验中，抑制H2228细胞的迁移。它不仅能够抑制野生型和大部分ALK突变体，还能克服原发耐药性，通过抑制SRC抑制转移性特征。在患者来源的移植瘤模型中，TPX-0005能够引起具有致瘤性ALK、ROS1和TRKC融合的肿瘤显著消退。此外，在一系列小鼠移植瘤模型中，TPX-0005不仅仅在含有野生型致瘤性靶标的肿瘤中具有显著的抗肿瘤活性，还能通过抑制相应靶标的磷酸化，在具有溶剂前沿突变（solvent front mutations）致癌基因的肿瘤中也发挥其效力。			2021/11/26	pj/sjz	D0111		
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 00:00:00	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		2023-05-26 00:00:00	SXZ	D0113	批准单位与名称修改	LXL非恶性肿瘤
SB202190											SB202190 (FHPI)是一种有效的p38 MAPK抑制剂，靶向作用于p38α/β，无细胞试验中IC50为50 nM/100 nM，有时用于代替SB 203580研究其在体内对SAPK2a/p38的潜在作用。SB202190 可通过诱导自噬和血红素氧化酶1来抑制内皮细胞的凋亡。SB202190可显著抑制Erastin依赖的铁死亡ferroptosis。SB202190显著抑制内源本底和和抗Fas抗体诱导的MAPKAPK 2活性，且抑制效果呈剂量依赖性。SB202190本身就足以诱导Jurkat细胞和Hela细胞的死亡：通过激活CPP 32样半胱氨酸蛋白酶，可阻断Bcl - 2的表达。p38β可减轻而p38α可加剧由SB202190诱导的细胞凋亡。在HaCaT细胞中SB202190强烈抑制由紫外线诱导的cox - 2蛋白表达和 mRNA水平。用SB202190处理肾小管上皮细胞（正常大鼠k肝脏-52E），可将由白蛋白引发的炎症（单核细胞趋化蛋白-1，MCP - 1）或肿瘤生长因子β-1（TGFβ-1）引发的原纤维化（原骨胶原I a1，procollagen-i alpha1）相关基因降低50%。SB202190处理A549细胞，可诱导JNK磷酸化（该磷酸化效应呈时间和剂量依赖性）、转录因子ATF - 2磷酸化，并增加AP – 1与DNA的结合。SB202190处理促进THP-1和MV4-11细胞的生长。SB202190可提高c-Raf 和ERK（细胞外信号调节激酶）磷酸化，暗示由SB202190诱导的白血病细胞增殖过程有Ras-Raf-MEK-mitogen激活的MAPK通路的参与。SB202190通过抑制p38减弱了由人脊髓灰质炎IgG（PV-IgG）在被动转移小鼠模型中诱发的水泡形成[5]。在脓毒症内毒素模型中，与对照组相比，经SB 202190处理可显著提高存活率。			2021/11/26		D0114		
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	2020-04-10 00:00:00	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		2023-05-26 00:00:00	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.	2015-07-24 00:00:00	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		2023-05-26 00:00:00	SXZ	D0118	批准单位与名称修改	LXL
Sorafenib	索拉非尼	Nexavar	多吉美	拜耳医药	2005/12/1	FDA/NMPA	NEXAVAR is a kinase inhibitor indicated for the treatment of：1.Unresectable hepatocellular carcinoma. 2.Advanced renal cell carcinoma. 3. Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment.	Sorafenib是一种激酶抑制剂，其适应症为：1.不可切除的肝细胞癌。2.晚期肾细胞癌。3.对放射性碘治疗无效的局部复发或转移性、进行性、分化型甲状腺癌(DTC)。2006年NMPA批准索拉非尼适用于肾细胞癌，肝细胞癌和甲状腺癌。	肝癌，肾癌，甲状腺癌	Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro. Sorafenib was shown to inhibit multiple intracellular (c-CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT- 3, RET, RET/PTC, VEGFR-1, VEGFR- 2, VEGFR- 3, and PDGFR-?). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis and apoptosis. Sorafenib inhibited tumor growth of HCC, RCC, and DTC human tumor xenografts in immunocompromised mice. Reductions in tumor angiogenesis were seen in models of HCC and RCC upon sorafenib treatment, and increases in tumor apoptosis were observed in models of HCC, RCC, and DTC.	索拉非尼是一种激酶抑制剂，可在体外降低肿瘤细胞增殖。索拉非尼可抑制多种细胞内（c-CRAF、BRAF和突变BRAF）和细胞表面激酶（KIT、FLT-3、RET、RET/PTC、VEGFR-1、VEGFR-2、VEGFR-3和PDGFR-?）的活性。其中一些激酶被认为与肿瘤细胞信号传导、血管生成和凋亡有关。索拉非尼抑制免疫功能低下小鼠中HCC、RCC和DTC人源肿瘤异种移植物的肿瘤生长。索拉非尼治疗后，HCC和RCC模型的肿瘤血管生成减少，HCC、RCC和DTC模型的肿瘤凋亡增加。	FDA-approval:07/2020;NMPA-approval:?2018	索拉非尼（Sorafenib）与多种细胞内（CRAF、BRAF和突变型BRAF）和细胞表面激酶（KIT、FLT-3、VEGFR-2、VEGFR-3和PDGFR-?）相互作用。这些激酶中有几种与血管生成有关，因此索拉非尼（Sorafenib）减少了肿瘤的血液供应。索拉非尼（Sorafenib）可独特靶向Raf/Mek/Erk途径。通过抑制这些激酶的活性，涉及细胞增殖和血管生成的基因转录受到抑制。	2023/6/20	sxz	D0119	修改日期；sxz	
Sotorasib	索托拉西布	Lumakras		Amgen Inc	2021/5/28	FDA	LUMAKRAS is an inhibitor of the RAS GTPase family indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), who have received at least one prior systemic therapy.	Sotorasib是一种RAS GTP酶家族蛋白抑制剂，适用于既往接受过至少一种全身治疗方案的携带KRAS G12C突变的局部晚期或转移性非小细胞肺癌成人患者。	非小细胞肺癌	Sotorasib is an inhibitor of KRASG12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRASG12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines. Sotorasib inhibited KRASG12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models sotorasib-treatment led to tumor regressions and prolonged survival and was associated with anti-tumor immunity in KRAS G12C models.	Sotorasib是KRAS G12C的抑制剂，G12C突变是KRAS基因的一种致癌突变，Sotorasib和G12C独特的半胱氨酸形成不可逆的共价键，将突变的KRAS蛋白处于非激活状态，从而抑制下游促癌信号通路的传导，且不影响野生型KRAS的功能。	05/2021		2021/11/26	pj/sjz	D0120		
Sunitinib	舒尼替尼	Sutent	索坦	Pfizer Italia S.R.I	2006/1/26	FDA/NMPA	SUTENT is a kinase inhibitor indicated for: 1.treatment of adult patients with gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate. 2.treatment of adult patients with advanced renal cell carcinoma (RCC). 3.adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy. 4.treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in adult patients with unresectable locally advanced or metastatic disease.	SUTENT是一种激酶抑制剂，其适应症为：1.甲磺酸伊马替尼治疗失败或不能耐受的胃肠间质瘤(GIST)成人患者。2.晚期肾细胞癌(RCC)成人患者。3.肾切除术后存在高复发风险的肾细胞癌成人患者的辅助治疗。4.不可切除的局部晚期或转移性的高分化进展期胰腺神经内分泌肿瘤(pNET)成人患者。2007年舒尼替尼首次获得NMPA批准，至2015年NMPA批准其适用于胃肠道间质瘤，肾细胞癌和胰腺神经内分泌肿瘤。	胃肠间质瘤、肾细胞癌、腺神经内分泌肿瘤	Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.Sunitinib inhibited the phosphorylation of multiple RTKs (PDGFRβ, VEGFR2, KIT) in tumor xenografts expressing RTK targets in vivo and demonstrated inhibition of tumor growth or tumor regression and/or inhibited metastases in some experimental models of cancer. Sunitinib demonstrated the ability to inhibit growth of tumor cells expressing dysregulated target RTKs (PDGFR, RET, or KIT) in vitro and to inhibit PDGFRβ- and VEGFR2-dependent tumor angiogenesis in vivo.	舒尼替尼（Sunitinib）是多种受体酪氨酸激酶(RTK)的小分子抑制剂，其中某些激酶与肿瘤的生长、病理性血管生成和肿瘤转移有关。舒尼替尼（Sunitinib）对多种激酶（> 80种激酶）的抑制活性已得到评价，已确定为以下受体的抑制剂：血小板衍生生长因子受体（PDGFRa和PDGFRb）、血管内皮生长因子受体（VEGFR1、VEGFR2和VEGFR3）、干细胞因子受体（KIT）、Fms样酪氨酸激酶3（FLT3）、集落刺激因子-1受体（CSF-1R）以及胶质细胞源性神经营养因子受体（RET）。生化和细胞试验证实舒尼替尼（Sunitinib）能抑制这些受体酪氨酸激酶（RTK）的活性，并且在细胞增殖试验中证明了舒尼替尼（Sunitinib）的抑制作用。生化和细胞试验表明舒尼替尼（Sunitinib）主要代谢物的活性与其相似。舒尼替尼（Sunitinib）在体内表达RTK的肿瘤异种移植物中可抑制多种 RTK（PDGFRβ、VEGFR2、KIT）磷酸化，并且在某些肿瘤实验模型中显示出抑制肿瘤生长或肿瘤消退和/或抑制转移。舒尼替尼（Sunitinib）在体外能够抑制表达失调RTK（PDGFR、RET或KIT）的肿瘤细胞的生长，并在体内抑制PDGFRβ和VEGFR2依赖性肿瘤血管生成。	FDA-approval:08/2021;NMPA-approval:?2015		2023/6/20	sxz	D0121		
Talazoparib	他拉唑帕尼	Talzenna		辉瑞	2018/10/16	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。	乳腺癌	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。	09/2021		2021/11/26		D0122		
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		
VX-970|Berzosertib										Berzosertib是一种ATR抑制剂，可以阻断ATR蛋白，而ATR蛋白可以帮助癌细胞修复受损的DNA。			Berzosertib（VX-970）已用于研究卵巢肿瘤、卵巢浆液性肿瘤、成人实体瘤、晚期实体瘤等治疗的试验中。	2021/11/26		D0138		
Mobocertinib	莫博赛替尼	Exkivity	安卫力	Takeda Pharms USA	2023-01-26 00:00:00	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		2023-05-26 00:00:00	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		
Savolitinib	赛沃替尼	Orpathys	沃瑞沙	合全药业	2021/6/22	NMPA		赛沃替尼是一种MET抑制剂，适用于含铂化疗后疾病进展或不耐受标准含铂化疗的、具有间质-上皮转化因子（MET）外显子14跳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		赛沃替尼可选择性抑制MET（Mesenchymal-epithelial transition factor，细胞-间质表皮转化因子）激酶的活性，可抑制MET激酶的磷酸化，对MET基因扩增以及MET 14号外显子跳变的肿瘤细胞增殖有明显的抑制作用。在多种MET异常的人源肿瘤裸鼠移植模型中，赛沃替尼对肿瘤生长具有抑制作用。	06/2021		2021/11/26	pj/sjz	D0142		
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		
BGJ398|Infigratinib													肺鳞癌、膀胱癌和胆管癌的基础研究。	2021/11/26	pj/sjz	D0146		
BAY 86-9766														2021/11/26	pj/sjz	D0147		
Camrelizumab	卡瑞利珠单抗		艾瑞卡	盛迪亚医药	2019/5/29	NMPA		卡瑞利珠单抗是一种人源化单克隆抗体，其适应症为：1.卡瑞利珠单抗用于既往接受过索拉非尼治疗和/或含奥沙利铂系统化疗的晚期肝细胞癌患者的治疗。2.卡瑞利珠单抗可联合培美曲塞和卡铂适用于表皮生长因子受体（EGFR）基因突变阴性和间变性淋巴瘤激酶（ALK）阴性的不可手术切除的局部晚期或转移性非鳞状非小细胞肺癌（NSCLC）的一线治疗。3.卡瑞利珠单抗用于既往接受过一线化疗后疾病进展或不可耐受的局部晚期或转移性食管鳞癌患者的治疗。	肝细胞癌，非小细胞肺癌，食管鳞癌		T 细胞表达的 PD-1 受体与其配体 PD-L1 和 PD-L2 结合，可以抑制 T 细胞增殖和细胞因子生成。部分肿瘤细胞的 PD-1 配体上调，通过这个通路信号传导可抑制激活的 T 细胞对肿瘤的免疫监视。注射用卡瑞利珠单抗是一种人类免疫球蛋白 G4（IgG4）单克隆抗体（HuMAb），可与 PD-1 受体结合，阻断其与 PD-L1 和 PD-L2 之间的相互作用，阻断 PD-1 通路介导的免疫抑制反应，包括抗肿瘤免疫反应。在同源小鼠肿瘤模型中，阻断 PD-1 活性可抑制肿瘤生长。卡瑞利珠单抗在临床研究中可见皮肤毛细血管增生，但机制尚不清楚。非临床研究显示，卡瑞利珠单抗与人 VEGFR2 虽然具有弱结合， KD 为 714 nM；卡瑞利珠单抗与药理作用靶点人 PD-1 结合的 KD 为 3.31 nM。	06/2020		2021/11/26	pj/sjz	D0149		
Sintilimab	信迪利单抗		达伯舒	信达生物	2018/12/24	NMPA		信迪利单抗是一种重组人源抗程序性死亡受体1单克隆抗体，其适应症为：1.至少经过二线系统化疗的复发或难治性经典型霍奇金淋巴瘤的治疗。2.信迪利单抗联合培美曲塞和铂类化疗，用于未经系统治疗的表皮生长因子受体（EGFR）基因突变阴性和间变性淋巴瘤激酶（ALK）阴性的晚期或复发性非鳞状细胞非小细胞肺癌的治疗。3. 信迪利单抗联合吉西他滨和铂类化疗，用于不可手术切除的晚期或复发性鳞状细胞非小细胞肺癌的一线治疗。4. 信迪利单抗联合贝伐珠单抗，用于既往未接受过系统治疗的不可切除或转移性肝细胞癌的一线治疗。	淋巴瘤、非小细胞肺癌、肝细胞癌		T 细胞表达的 PD-1 受体与其配体PD-L1 和 PD-L2 结合，可以抑制T 细胞增殖和细胞因子生成。部分肿瘤细胞的 PD-1 配体上调，通过这个通路信号传导可抑制激活的 T 细胞对肿瘤的免疫监视。信迪利单抗是一种人类免疫球蛋白G4（IgG4）单克隆抗体（HuMAb），可与PD-1 受体结合，阻断其与PD-L1和 PD-L2 相互作用介导的免疫抑制反应，增强抗肿瘤免疫效应。在小鼠肿瘤模型中，阻断 PD-1 通路活性可抑制肿瘤生长。	06/2021		2021/11/26	pj/sjz	D0150		
Tislelizumab	替雷利珠单抗		百泽安	百济神州	2019/12/26	NMPA		替雷利珠单抗是一种针对程序性死亡受体-1（PD-1)D的人源化单克隆抗体（IgG4变体）其适应症为：1.至少经过二线系统化疗的复发或难治性经典型霍奇金淋巴瘤的治疗。2. PD-L1 高表达的含铂化疗失败包括新辅助或辅助化疗 12 个月内进展的局部晚期或转移性尿路上皮癌的治疗。3.适用于既往经治的局部晚期不可切除或转移性高度微卫星不稳定型（MSI-H）或错配修复缺陷型（dMMR）实体瘤	霍奇金淋巴瘤、尿路上皮癌		替雷利珠单抗是一种人源化重组抗 PD-1 单克隆抗体。T 细胞表达的 PD-1 受体与其配体 PDL1 和 PD-L2 结合，可以抑制 T 细胞增殖和细胞因子生成。部分肿瘤细胞的 PD-1 配体上调，通过这个通路信号传导可抑制激活的 T 细胞对肿瘤细胞的免疫监视。	04/2020		2022/4/12	sxz	D0151		
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
Taletrectinib|AB-106	他雷替尼												taletrectinib已经在日本和美国完成了1期临床试验，用于治疗含有ROS1或NTRK融合基因实体瘤患者。根据临床前研究的结果，AB-106对于ROS1 G2032R和L2026M突变敏感，同时具有较好的入脑性，适合治疗克唑替尼耐药后的患者。	2021-11-26 00:00:00	pj/sjz	D0155	药物名称更新	LXL
Acalabrutinib	阿可替尼	Calquence	康可期	AstraZeneca Pty Ltd	2017-10-31 00:00:00	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		2023-05-26 00:00:00	SXZ	D0156	批准单位与名称修改	LXL
AZD1775													治疗铂类敏感的TP53突变的卵巢癌患者的研究正在进行中。用于卵巢癌 恶性黑色素瘤乳腺癌 头颈部癌 结直肠癌 小肠癌 皮肤癌的基础研究	2021/11/26	pj/sjz	D0157		
Rociletinib|CO-1686											Rociletinib有效且选择性地抑制表达突变型EGFR的NSCLC细胞的生长并诱导细胞凋亡。罗替替尼耐药的NSCLC细胞系对AKT抑制敏感。 Rociletinib在人EGFR-L858R和表达EGFR-L858R-T790M的转基因小鼠中显示出抗肿瘤活性。			2021/11/26	pj/sjz	D0158		
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		2022-01-24 00:00:00	sxz	D0160	修改日期；sxz	LXL
Olverembatinib	奥雷巴替尼			广州顺健生物医药科技有限公司	1905/7/13	NMPA		奥雷巴替尼（Olverembatinib）是小分子蛋白酪氨酸激酶抑制剂,用于治疗T315I突变的慢性髓细胞白血病慢性期或加速期的成年患者。	慢性髓细胞白血病		奥雷巴替尼（Olverembatinib）是小分子蛋白酪氨酸激酶抑制剂，可有效抑制Bcr-Abl酪氨酸激酶野生型及多种突变型的活性，抑制Bcr-Abl酪氨酸激酶及下游蛋白STAT5和Crkl的磷酸化，阻断下游通路活化，诱导Bcr-Abl阳性、Bcr-Abl T315I突变型细胞株的细胞周期阻滞和调亡。			2022/1/24	sxz	D0161		
PF-477736											PF-477736是一种ATP竞争性chk1抑制剂，作用于CA46和HeLa细胞，废除Camptothecin诱导的DNA损伤检查点，这种作用具有剂量依赖性。PF-477736作用于HT29细胞，有效废除Gemcitabine诱导的S期停滞，使凋亡细胞群相应增加。PF-477736作用于Gemcitabine停滞的细胞，诱导H2AX磷酸化强度剧增，DNA损伤位点附近产生大量的γ-H2AX分子。PF-477736作用于HL-60细胞，在Curcumin存在时，选择性抑制p73和p53磷酸化。PF-477736(360nM)作用于COLO205细胞，抑制Docetaxel诱导的组蛋白H3(Ser10)和Cdc25C(Ser216)磷酸化，且增强凋亡。PF-477736(250nM)与MK-1775联用作用于OVCAR-5细胞，具有显著的协同细胞毒性。PF-477736与MK-1775联用作用于OVCAR-5细胞，DNA复制结束前产生过早的有丝分裂，受损的DNA导致细胞凋亡。PF477736按Gemcitabine的最大耐受剂量处理携带Colo205移植瘤的小鼠模型，增强抗肿瘤活性，这种作用具有剂量依赖性。PF-477736处理携带Colo205移植瘤的小鼠模型，诱导组蛋白H3(Ser10)磷酸化和磷酸化组蛋白H2AX增加。		CDKN2A是一种重要的抑癌基因，属于细胞周期依赖性激酶抑制因子基因家族，CDKN2A基因通过可变剪切可产生不同的转录本，至少编码3个不同的蛋白，编码两种周期的抑制蛋白,发挥细胞周期调控作用，从而控制细胞从G1期转到S期，CDKN2A基因突变或缺失与多种肿瘤相关，是一个非常重要的抑癌基因。在一项临床前研究中，Chk1抑制剂PF-477736和MK2抑制剂PF3644022协同抑制携带CDKN2A缺失的多个癌细胞系和CDKN2A缺失的转化细胞的生长。	2022/1/24	sxz	D0162		
PF3644022											PF-3644022是一种有效的、可逆的ATP竞争性MAPKAPK2(MK2)抑制剂。		CDKN2A是一种重要的抑癌基因，属于细胞周期依赖性激酶抑制因子基因家族，CDKN2A基因通过可变剪切可产生不同的转录本，至少编码3个不同的蛋白，编码两种周期的抑制蛋白,发挥细胞周期调控作用，从而控制细胞从G1期转到S期，CDKN2A基因突变或缺失与多种肿瘤相关，是一个非常重要的抑癌基因。在一项临床前研究中，Chk1抑制剂PF-477736和MK2抑制剂PF3644022协同抑制携带CDKN2A缺失的多个癌细胞系和CDKN2A缺失的转化细胞的生长。	2022/1/24	sxz	D0163		
R3Mab													在一项临床前研究中，R3Mab抑制了培养物中转化FGFR3 S249C的细胞增殖。	2022/1/24	sxz	D0164		
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		
SAR125844											SAR125844是一种有效的、高选择性的Met(c-Met)激酶抑制剂，对野生型Met(c-Met)激酶具有纳摩尔级活性(IC50=4.2nM)，在两种MET扩增的人源胃肿瘤移植模型中，静脉注射SAR125844可引起有效的MET激酶抑制作用，对下游PI3K/AKT和RAS/MAPK通过具有显著的影响。		在一项I期临床试验中，携带MET扩增的晚期实体瘤（包括非小细胞肺癌患者）患者使用SAR125844治疗后耐受性良好，获得部分缓解的患者占17%(5/29），获得疾病稳定的患者占17%（17/29）。	2022/1/24	sxz	D0167		
Nimotuzumab	尼妥珠单抗		泰欣生	百泰生物药业有限公司	1905/7/9	NMPA		尼妥珠单抗是中国第一个人源化单抗药物，NMPA批准尼妥珠单抗用于治疗携带EGFR表达阳性的III/IV期鼻咽癌患者。	鼻咽癌		尼妥珠单抗可阻断EGFR与其配体的结合，并对EGFR过度表达的肿瘤具有抗血管生成，抗细胞增殖和促凋亡作用。	2008/1/1		2022/1/24	sxz	D0168		
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		
RO4987655											CTEP(RO4956371)是一种高效，高选择性的MEK抑制剂。		在一项I期试验中,使用RO4987655，11％（2/18）的KRAS突变的NSCLC患者获得了部分缓解。	2022/1/24	sxz	D0170		
RG7112											RG7112是有效的选择性MDM2拮抗剂，是一种Nutlin家族成员。RG7112以高亲和力结合MDM2，阻断其与p53在体外的相互作用。RG7112–MDM2复合物的晶体结构表明，小分子结合到MDM2的p53口袋，模拟重要p53氨基酸残基的相互作用。RG7112治疗表达野生型p53的癌细胞，能够激活p53通路，导致细胞周期阻滞和细胞凋亡。RG7112对一组肿瘤细胞系表现出有效的抗肿瘤活性。然而，其抗凋亡活性大相径庭，在MDM2基因扩增的骨肉瘤细胞中观察到最优反应。		有研究表明，RG7112对实体瘤细胞具有抗肿瘤活性，且在MDM2扩增的肉瘤细胞中反应最佳，突变模型的小鼠口服无毒浓度的RG7112可对肿瘤产生抑制或消退的作用。	2022/1/24	sxz	D0171		
Dalpiciclib	达尔西利			江苏恒瑞医药	2021/12/1	NMPA		达尔西利（Dalpiciclib）是一种周期蛋白依赖性激酶4和6（CDK4和CDK6）抑制剂,联合氟维司群用于激素受体（HR）阳性，人表皮生长因子受体2（HER2）阴性的经内分泌治疗后进展的复发或转移性乳腺癌的治疗。	乳腺癌		达尔西利（Dalpiciclib）是一种周期蛋白依赖性激酶4和6（CDK4和CDK6）抑制剂，可降低CDK4和CDK6信号通路下游的视网膜母细胞瘤蛋白磷酸化水平，并诱导细胞G1期阻滞，从而抑制肿瘤细胞的增殖。	12/2021		2022/1/29	sxz	D0172		
Bemcentinib									非小细胞肺癌		AXL是STK11/LKB1突变型非小细胞肺癌免疫抑制的关键靶向驱动因子，促进了免疫抑制检查点(CPI)的耐药。STK11/LKB1突变型NSCLC缺乏TCF1表达的CD8+T淋巴细胞，Bemcentinib对AXL的系统抑制作用增强了树突状细胞分泌的I型干扰素，使肿瘤相关的TCF1 + PD-1 + CD8 T 细胞扩增，并恢复了PD-1的治疗反应		一项临床试验的研究表明，AXL抑制剂bemcentinib联合pembrolizumab使3名携带STK11/LKB1突变的NSCLC患者表现出客观的临床反应和临床获益（PMID:NCT03184571; NCT03184571)。	2022/1/29	sxz	D0173		
Fluzoparib	氟唑帕利胶囊		艾瑞颐	江苏恒瑞医药股份有限公司	2020/12/11	NMPA		Fluzoparib适应症为:1.适用于既往经过二线及以上化疗的伴有胚系BRCA突变(gBRCAm)的铂敏感复发性卵巢癌、输卵管癌或原发性腹膜癌患者的治疗。2.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。	卵巢癌、输卵管癌、原发性腹膜癌		氟唑帕利为小分子PARP抑制剂，对PARP1酶分子水平抑制作用的IC50值为2.0nM，对MDA-MB-436细胞PARP1酶活性抑制作用的IC50值为8.0nM。氟唑帕利可抑制BRCA1/2功能异常细胞中的DNA修复过程，诱导细胞周期阻滞，进而抑制肿瘤细胞增殖。	02/2021		2022/1/29	sxz	D0174		
Ribociclib	瑞波西利	Kisqali	凯丽隆	Novartis Pharma Schweiz AG	2017-03-13 00:00:00	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		2023-05-26 00:00:00	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		
Patritumab Deruxtecan				Daiichi Sankyo, Inc（第一三共（中国）投资有限公司）									patritumab deruxtecan （U3-1402）是一种靶向HER3的抗体药物偶联物（ADC），FDA授予Patritumab Deruxtecan突破性疗法认定，用于第三代酪氨酸激酶抑制剂（TKI）和铂类治疗期间或之后疾病进展的转移性或局部晚期 EGFR 突变的非小细胞肺癌患者。	2022/3/23	sxz	D0177		
CLN-081								美国FDA授予EGFR抑制剂CLN-081突破疗法认定，用于治疗接受过铂类全身化疗，且具有EGFR外显子20插入突变的局部晚期或转移性非小细胞肺癌患者。			TAS6417 (CLN-081, TPC-064)是一种新型的EGFR抑制剂，靶向EGFR突变体，对野生型EGFR抑制效力较低，对临床相关的EGFR突变（包括ins20）具有广泛的活性。			2022/3/23	sxz	D0178		
Cadonilimab	卡度尼利单抗		开坦尼	康方药业有限公司	2022/6/28	NMPA	卡度尼利单抗为我国自主研发的创新双特异性抗体，适用于既往接受含铂化疗治疗失败的复发或转移性宫颈癌患者的治疗。				卡度尼利单抗注射液是一种靶向人PD-1和CTLA-4的双特异性抗体，可阻断PD-1和CTLA-4与其配体PD-L1/PD-L2和B7.1/B7.2的相互作用，从而阻断PD-1和CTLA-4信号通路的免疫抑制反应，促进肿瘤特异性的T细胞免疫活化，进而发挥抗肿瘤作用。			2022/7/20	sxz	D0179		
Seralutinib													Seralutinib (PK10571, GB002) 是一种新型PDGFR激酶抑制剂，Seribantumab是一种完全人源抗HER3 IgG2单克隆抗体，可在NRG1融合驱动的临床前模型中抑制肿瘤生长。	2022/7/20	sxz	D0180		
PC14586											PC14586是一种新型小分子p53重激活剂，可选择性地与p53 Y220C突变蛋白结合并恢复p53野生型构象和转录活性，从而产生有效的临床前抗肿瘤活性		。PC14586在临床前物种中耐受性良好，并具有良好的发展特征。PC14586的安全性和有效性目前正在一项I / II期临床研究中进行评估。临床研究确定局部晚期或转移性TP53 Y220C突变实体瘤的成人患者最大耐受剂量和推荐的2期剂量，结果表明，在21个符合条件的患者中5名患者观察到PR现象，3个最高剂量组中10个符合条件的患者有3个PR和7个SD。且观察到携带P53 Y220C突变的循环肿瘤DNA和周肿瘤数量均下降。（Abstract: Dumbrava et al. Abstract# 3003, ASCO 2022; Abstract: Dumble et al. Abstract# LB006, AACR 2021）	2022/11/8	sxz	D0181		
RLY-2608											RLY-2608是一种新型变构、泛突变、选择性PI3Kα抑制剂,一项临床I期研究正在评估RLY-2608作为单药在PI3KCA突变的晚期实体瘤患者( pts )中的临床活性，以及联合氟维司群在PIK3CA突变、HR +、HER2 -转移性乳腺癌( MBC )患者中的临床活性。			2022/11/8	sxz	D0182		
LOXO-783											LOXO-783是一种高活性、突变选择性和脑渗透性的PI3Kα H1047R变构抑制剂，一项临床前实验证明LOXO-783有效且选择性地抑制H1047R突变型。			230602	pj	D0183	名称修订	LXL
RP-6306													RP-6306是一种蛋白激酶，膜相关酪氨酸/苏氨酸1 抑制剂	2022/11/8	sxz	D0184		
BLU-222													BLU-222是一种CDK2（细胞周期蛋白依赖性激酶）选择性抑制剂，一项临床前研究证明，BLU-222对携带CCNE1（（细胞周期蛋白E1）扩增的细胞系具有高度敏感性，且在体外研究中BLU-222对携带CCNE1扩增的异种移植（CDX）肿瘤模型具有显著的抗肿瘤活性	2022/11/8	sxz	D0185		
RMC-6236																D0186		
Telisotuzumab Vedotin													Telisotuzumab Vedotin是由c-Met抗体（ABT-700）和微管抑制剂（单甲基奥利他汀E）组成的抗体-药物偶联物.Telisotuzumab Vedotin正在临床试验NCT02099058（一项评估ABBV-399在晚期实体瘤受试者中的安全性，药代动力学（PK）和初步疗效的研究）中进行了研究。			D0187		
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	
Sitravatinib|MGCD516				Mirati Therapeutics							Sitravatinib（MGCD516）是一种选择性激酶抑制剂，可有效抑制受体酪氨酸激酶(RTK)，其中包括TAM家族受体(TYRO3、Axl、Mer)、Split家族受体(VEGFR2、KIT)以及RET。Sitravatinib可以靶向消除免疫抑制性的M2型巨噬细胞（M2 TAM）、调节性T细胞（Treg）、骨髓来源的抑制性细胞(MDSC)，增加树突状细胞(DC)的抗原呈递能力，从而增强免疫系统的抗肿瘤效应，因此Sitravatinib联合PD-1单抗有可能克服免疫治疗耐药。		Sitravatinib正在多项用于治疗接受PD-1免疫疗法治疗后复发的癌症患者的临床试验中被评估，包括一项正在开展患者入组的潜在注册性的Sitravatinib联合一款检查点抑制剂用于治疗非小细胞肺癌(NSCLC)患者的III期试验。	2023/4/25	pj	D0189	新增	sxz
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
Selitrectinib|LOXO-195													"Selitrectinib(LOXO-195)是拜耳公司和Loxo公司合作开发的第二代TRK抑制剂，用于对抗TRK激酶区的耐药突变。尽管NTRK融合激酶阳性患者对拉罗替尼响应持续时间较长，但一定时间后大多数患者还是出现由于NTRK突变而产生的获得性耐药现象。目前观察到的突变主要是激酶溶剂前沿 G595R（TRKA）和 G623R （TRKC）以及DFG 部分的 G667C（TRKA）。拉罗替尼末端的吡咯环和苯环与突变后的TRKs产生较大的位阻效应，导致亲和力大大下降。基于以上结构特性，研究人员经过大量筛选，发现大环化合物LOXO-195可以保留其他作用力的同时有效降低位阻效应，从而大大提高亲和力。AACR 2019年会报道了31例NTRK靶向药耐药患者接受LOXO-195治疗的疗效和安全性数据，其中20例患者来自LOXO-195的I期临床试验，11例患者来自同情用药计划。LOXO-195治疗 ""溶剂前沿突变""（Solvent Front）的客观缓解率(ORR)达50%。而对不依赖于NTRK基因的旁路突变（bypass）则无效。最常见的治疗相关不良反应是头晕/共济失调（65％），恶心/呕吐（50％），贫血（30％），肌痛，腹痛，疲劳和淋巴细胞减少（均为20％）。"	20230602	pj	D0191	新增药物	LXL
ABI-009													FYARRO?（ABI-009）是西罗莫司白蛋白结合型纳米颗粒注射用混悬液，2014年从新基获得该药的授权许可。西罗莫司，又称雷帕霉素，是一种大环内酯抗生素类免疫抑制剂，为mTOR 特异性抑制剂。mTOR是一类丝/苏氨酸激酶，细胞内存在mTORC1和mTORC2两种复合体，其信号通路的稳定性会影响T细胞中细胞因子的表达，并参与免疫抑制，影响DNA转录，调节细胞的生长与凋亡。白蛋白具有生物相容性好、无毒、无免疫原性等特点，以其为载体的纳米药物在肿瘤靶向上具有独特的优势。与已上市的mTOR抑制剂相比，FYARRO?具有更优越的PK特性、更宽的治疗窗、更高的肿瘤组织药物暴露量、更强的靶细胞抑制作用以及更理想的安全性。此前，该药曾被FDA授予晚期恶性PEComa的突破性疗法认定、孤儿药资格和快速审评通道。	230602	pj	D0192	补充药物	
Glumetinib	谷美替尼		海益坦	海和药物	2023/3/7	NMPA		2023年NMPA批准用于适用于具有间质-上皮转化因子（MET）外显子14跳变的局部晚期或转移性非小细胞肺癌（NSCLC）的治疗。上述适应症是基于一项单臂临床试验结果给予的附条件批准。本适应症的完全批准将取决于后续开展的确证性试验的临床获益。	非小细胞肺癌				2023年3月，海益坦?谷美替尼片（研发代号：SCC244）获得国家药品监督管理局（NMPA）批准在中国获得附条件批准上市。用于治疗具有间质-上皮转化因子（MET）外显子14跳跃突变（METex14跳变）的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。谷美替尼是一款口服、强效、高选择性小分子MET抑制剂。临床前研究显示谷美替尼片可强效和特异性靶向抑制MET激酶活性。临床研究结果显示，谷美替尼片具有优良的药代动力学特性以及良好的安全性和耐受性，在具有MET改变的晚期非小细胞肺癌患者中显示了明确疗效且脑转移患者同样获益。截止本新闻发布日期为止，与已上市同类产品相比，谷美替尼片稳态谷浓度比同类产品更高，可以持续抑制靶点; 半衰期长，适合每日一次给药; 不需要根据体重做剂量调整; 药物相互作用少，合并用药安全性风险低。谷美替尼片已被美国食品药品监督管理局（FDA）授予具有MET基因变异的非小细胞肺癌孤儿药资格（Orphan Drug Designation, ODD）。	230602	pj	D0193	补充药物	LXL添加适应症（中文
Seribantumab													2022年5月25日Elevation Oncology宣布，美国食品药品监督管理局（FDA）已经授予该公司HER3单抗seribantumab快速通道（Fast Track）资格，用于治疗携带NRG1基因融合的晚期实体瘤。Seribantumab是一种全人源性 IgG2单克隆抗体，可与人表皮生长因子受体3（ERBB3/HER3）结合。HER3传统上通过与其主要配体 neuregulin-1（NRG1）的结合来激活。NRG1基因融合是一种罕见的基因组改变，它将 NRG1与其相关蛋白结合以产生嵌合 NRG1“融合蛋白”，融合后引发HER3过度激活，从而驱动肿瘤生长和癌细胞存活。NRG1融合已在多种实体肿瘤中发现，包括肺、胰腺、胆囊、乳腺、卵巢、结直肠、神经内分泌瘤、胆管癌和肉瘤，目前还没有针对NRG1融合阳性肿瘤的获批靶向疗法。此外，患有NRG1融合肿瘤的患者通常预后不良，使用标准疗法的结果较差。在临床前实验中，seribantumab阻止了含有 NRG1基因融合的细胞中HER3信号的激活，并破坏了整个ERBB家族信号通路的稳定性，包括HER2、EGFR和 HER4的激活。	230602	pj	D0194	补充药物	LXL
Avutometinib|VS-6766													Avutometinib是一种RAF/MEK钳制剂，可激发MEK与ARAF、BRAF和CRAF的非活性复合物，通过最大限度地抑制RAS途径，可能产生更完整和持久的抗肿瘤反应。与其他MEK抑制剂不同的是，该药具有同时阻断MEK激酶活性和RAF磷酸化MEK的能力。这种独特的机制使该药能够阻断MEK信号，而不会出现似乎限制其他抑制剂疗效的MEK的补偿性激活。Defactinib是一种口服的、耐受性好的、强效的ATP竞争性FAK抑制剂，当与Avutometinib联合使用时，能促进更强的肿瘤消退。该药在美国、欧盟和澳大利亚被授予治疗卵巢癌和间皮瘤患者的孤儿药称号。用Avutometinib+Defactinib治疗KRAS突变的实体瘤的临床前模型显示，该联合疗法在几个KRAS突变的肿瘤细胞系中具有协同作用。2期RAMP 201试验的中期数据显示，Avutometinib+Defactinib的联合治疗在患有严重预处理的复发性低级别卵巢浆液性癌患者中产生了令人鼓舞的反应率和良好的耐受安全性。	230602	pj	D0195	补充药物	LXL
Defactinib													Defactinib是一种口服的、耐受性好的、强效的ATP竞争性FAK抑制剂，当与Avutometinib联合使用时，能促进更强的肿瘤消退。该药在美国、欧盟和澳大利亚被授予治疗卵巢癌和间皮瘤患者的孤儿药称号。用Avutometinib+Defactinib治疗KRAS突变的实体瘤的临床前模型显示，该联合疗法在几个KRAS突变的肿瘤细胞系中具有协同作用。2期RAMP 201试验的中期数据显示，Avutometinib+Defactinib的联合治疗在患有严重预处理的复发性低级别卵巢浆液性癌患者中产生了令人鼓舞的反应率和良好的耐受安全性。	230602	pj	D0196	补充药物	LXL
Sutetinib	苏特替尼												苏特替尼是一种针对罕见EGFR敏感突变（包括G719X、S768I、L861Q）的国产靶向药，目前一项马来酸苏特替尼胶囊治疗局部晚期或转移性非小细胞肺癌（仅限非耐药性罕见EGFR突变，L861Q、G719X和/或S768I）的II期临床试验正在招募患者中（NCT05168566）。	230517	pj	D0197	新增药物	LXL
Befotertinib|D0316	贝福替尼		赛美纳	贝达药业	2023/5/31	NMPA		该药适用于既往经表皮生长因子受体（EGFR）酪氨酸激酶抑制剂治疗出现疾病进展，并且伴随EGFR T790M 突变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		甲磺酸贝福替尼是第三代表皮生长因子受体酪氨酸激酶抑制剂，能够选择性地抑制EGFR敏感突变和EGFR T790M耐药突变激酶。		甲磺酸贝福替尼胶囊是一种第三代EGFR-TKI，含有新的结构明确的、具有药理作用的化合物，属于“境内外均未上市的创新药”，其注册分类为化学药品1类，其有望用于治疗具有T790M突变及其他突变的EGFR阳性肺癌患者。	230517	pj	D0198	新增药物	LXL
Lazertinib|YH25448	拉泽替尼												Lazertinib（YH25448，商品名LECLAZA）是韩国柳韩洋行（Yuhan）研发的第三代EGFR酪氨酸激酶抑制剂，韩国之外的权益已转让给美国强生旗下的杨森制药。2021年1月18日，韩国食品药品管理局（MFDS）批准Lazertinib用于既往接受过EGFR-TKI治疗的EGFR T790M突变阳性局部晚期或转移性非小细胞肺癌患者的治疗。美国2020年3月11日Lazertinib获FDA突破性疗法认定。	230517	pj	D0199	新增药物	LXL
Oritinib|SH-1028	奥瑞替尼												甲磺酸奥瑞替尼片（SH-1028片）是南京圣和主研发的第三代EGFR酪氨酸激酶抑制剂（EGFR-TKI），不可逆地结合于突变形式的EGFR（T790M、L858R和19外显子缺失），主要作用在EGFR的激酶结构域，竞争性结合于激酶上的ATP位点，抑制EGFR的磷酸化过程，阻断下游信号通路的激活。2021年12月28日，CDE官网显示，南京圣和药业1类新药甲磺酸奥瑞替尼片上市申请获NMPA受理。	230517	pj	D0200	新增药物	LXL
Rezivertinib|BPI-7711	瑞泽替尼												瑞泽替尼是一款不可逆、高选择性的第三代小分子表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），对 EGFR 敏感突变及 EGFR T790M 耐药突变具有显著的抑制活性。2021年5月7日，上海倍而达药业三代EGFR抑制剂瑞泽替尼（BPI-7711）的上市申请获得NMPA受理。	230517	pj	D0201	新增药物	LXL
Limertinib|ASK120067													Limertinib(ASK120067)是高选择性、不可逆第三代EGFR-TKI，主要用于既往EGFR-TKI治疗时或治疗后出现疾病进展、并且经检测确认存在EGFRT790M突变阳性的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者的治疗。2021年11月16日，江苏奥赛康药业有限公司为1类新药「ASK120067片」递交的上市申请获CDE受理。	230517	pj	D0202	新增药物	LXL
Sunvozertinib|DZD9008	舒沃替尼												舒沃替尼是迪哲自主研发的一款口服、针对多种EGFR突变亚型的高选择性酪氨酸激酶抑制剂（TKI），是迄今为止肺癌领域首个且唯一获中美双“突破性疗法认定”的国创新药，也是首个获上市受理的、针对EGFR exon20ins突变型晚期NSCLC 的中国原研创新药。	230517	pj	D0203	新增药物	LXL修改研究现状
Unecritinib|TQ-B3101	优克替尼												Unecritinib(TQ-B3101)是一种新型的以ALK，ROS1和MET为靶点的小分子受体酪氨酸激酶抑制剂，临床前研究表明它有很好的抗肿瘤活性和持续作用时间。2022年6月，Unecritinib的上市申请获国家药品监督管理局受理。	230517	pj	D0204	新增药物	SXZ
Iruplinalkib|WX-0593	依鲁奥克												依鲁奥克片是齐鲁制药自主研发的新型ALK/ROS1抑制剂，代号为WX-0593。WX-0593可抑制不同融合类型的野生型以及ALK抑制剂耐药突变的ALK激酶活性，同时可有效抑制不同融合类型ROS1激酶的活性。2021年7月24日CDE官网显示，齐鲁制药1类新药依鲁奥克片的上市申请已获国家药监局受理。	230517	pj	D0205	新增药物	SXZ
Envonalkib|TQ-B3139	依奉阿克												依奉阿克（Envonalkib, TQ-B3139）是一种新型小分子ALK/ROS1/c-MET抑制剂，具有CNS渗透性。临床前研究及1期试验表明，对于ALK阳性NSCLC患者，Envonalkib耐受性良好且具备抗肿瘤活性。	230517	pj	D0206	新增药物	SXZ
Zotizalkib|TPX-0131													Zotizalkib(TPX-0131)是一种有效、选择性、CNS渗透性和口服活性的野生型ALK抑制剂和ALK耐药突变如G1202R、L1196M。	230522	pj	D0207	新增药物	SXZ
NVL-655													NVL-655是一种新型脑部渗透性、ALK选择性抑制剂，被设计用于对第一代、第二代和第三代ALK抑制剂产生耐药性的肿瘤，包括具有溶剂前沿G1202R突变或G1202R/L1196M、G1202R/G1269A或G1202R/L1198F复合突变的肿瘤。NVL-655针对中枢神经系统（CNS）渗透性进行了优化，以改善CNS转移患者的治疗选择。	230522	pj	D0208	新增药物	SXZ
NVL-520													NVL-520是一种强效、高选择性的新一代小分子ROS1抑制剂，不仅可以克服ROS1耐药突变，而且具备高血脑屏障穿透能力，同时因其ROS1靶点对NTRK的选择性非常高，避免了抑制NTRK带来的中枢神经毒性。	230522	pj	D0209	新增药物	SXZ
NVL-330													NVL-330是一种新型的脑渗透性HER2选择性酪氨酸激酶抑制剂，旨在治疗由HER2ex20驱动的肿瘤，避免由于野生型EGFR的脱靶抑制而导致的治疗限制性不良事件，以及治疗脑转移瘤。NVL-330高选择性靶向HER2，减少由于结构相关的野生型EGFR激酶抑制导致的相关潜在剂量限制性不良事件（如皮疹和胃肠道毒性）。此外，NVL-330已针对脑外显率进行了优化，以潜在地改善脑转移瘤患者的治疗选择。	230522	pj	D0210	新增药物	SXZ
Abivertinib|AC0010	艾维替尼												Abivertinib是艾森医药自主研发的靶向EGFR敏感突变（19del、L858R）和T790M突变的三代EGFR-TKI。2014年9月，同时获NMPA和FDA临床试验批准；2018年6月，艾维替尼完成中国注册临床研究，并向NMPA递交上市申请，同年8月被纳入优先审评。	230531	pj	D0211	新增药物	SXZ
Nazartinib|EGF816													Nazartinib (EGF816)是一个新的、突变选择性的三代EGFR靶向药，可阻断19del、21L858R及T790M等突变靶点。临床前研究显示，Nazartinib在动物模型中显示了更强的肿瘤退缩能力。该药于2016年5月获准在韩国使用，治疗T790M突变阳性的非小细胞肺癌。	230531	pj	D0212	新增药物	SXZ
Zorifertinib|AZD3759													Zorifertinib是一个专为治疗晚期NSCLC伴中枢神经系统（CNS）转移患者设计的新一代EGFR-TKI药物，具有高达100%的血脑屏障透过率，目前正在EGFR突变阳性NSCLC伴CNS转移患者中开展2/3期临床研究。	230531	pj	D0213	新增药物	SXZ
TQB3804													TQB3804是由正大天晴研发的第四代EGFR抑制剂，不仅能克服三代药物耐药后产生的两大类常见三重突变（Del19/T790M/C797S或L858R/T790M/C797S），更能抑制EGFR野生型和前二代靶向药物引发的T790M突变。临床前研究显示：TQB3804对d746-750(19del)/T790M/C797S、L858R/T790M/C797S、d746-750/T790M及L858R/T790M的二重及三重突变均有较强的抑制能力。在19del/T790M/C797S的不同动物模型中也能较好地延缓肿瘤的增长。目前正在开展I期临床研究（NCT04128085）。	230531	pj	D0215	新增药物	SXZ
BLU-945													BLU-945是第四代EGFR-TKIs中发展最为迅速的一种，前期 SYMPHONY临床试验中，33名 EGFR基因突变 NSCLC病人经BLU-945治疗后，肿瘤体积显著减小，1名病人获得了部分缓解（PR)，且安全性较好。ctDNA检测发现，T790M、C797S基因在癌组织中的表达显著下降，其中3个已达完全消除标准。	230531	pj	D0216	新增药物	SXZ
JBJ-04-125-02													JBJ-04-125-02是在EAI045基础上优化筛选得到的高药、低毒的小分子变构抑制剂，抑制活性更强。JBJ-04-125-02克服了EAI045须联用西妥昔单抗治疗的问题，实现了单独使用，同时增强了C797S基因突变的抑制能力。临床前研究表明，JBJ-04-125-02单药显示较好的肿瘤抑制效果。与EAI045联合西妥昔单抗相比，JBJ-04-125-02联合奥希替尼抗肿瘤活性更强，在多种小鼠模型中均能更有效地抑制肿瘤的生长。	230531	pj	D0217	新增药物	SXZ
JND3229													JND3229是一种可逆性的EGFR C797S抑制剂，对EGFR L858R/T790M/C797S、EGFR WT和EGFR L858R/T790M的IC50值分别为5.8、6.8和30.5 nM。JND3229具有较好的抗增殖活性，能有效地抑制体内肿瘤的生长。JND3229可用于癌症，尤其是非小细胞癌的研究。	230531	pj	D0218	新增药物	SXZ
CLN-081|TAS6417													TAS6417（现用名CLN-081）是日本大鹏制药研发的一款小分子EGFR抑制剂，授权给美国Cullinan Oncology公司。在2020年ESMO上公布了CLN-081（TAS6417）的首个人体、1/2a期临床试验（NCT04036682）的中期结果。	230531	pj	D0219	新增药物	SXZ
CH7233163													CH7233163是由罗氏公司(Roche)旗下中外制药(CHUGAI)研发的针对EGFR Del19/T790M/C797S三重突变的四代靶向药。与奥希替尼不同的是，CH7233163以非共价键结合方式作用于EGFR del19、L858R和T790M，并不受C797S突变的干扰。临床前研究显示：CH7233163在 EGFR Del19/L858R/T790M、L858R/T790M和Del19突变的小鼠上均可明显观察到肿瘤体积的缩小。	230531	pj	D0220	新增药物	SXZ
RX518|CK-101													RX518是一种新颖的、高选择性、高活性、不可逆的第三代EGFR-TKI，能够选择性抑制EGFR敏感型突变（21号外显子L858R突变和19号外显子缺失）和EGFR T790M耐药型突变，对野生型EGFR抑制作用很弱，临床上拟用于治疗EGFR突变阳性的非小细胞肺癌。	230531	pj	D0221	新增药物	SXZ
ZN-e4													ZN-e4是由Zentalis Pharmaceuticals公司开发的不可逆EGFR抑制剂，可有效抑制突变的EGFR，包括T790M耐药突变。Zentalis将ZN-e4设计为对突变型EGFR具有高度选择性，并且在临床前研究中观察到ZN-e4的使用不会产生针对野生型EGFR的代谢产物，还设计了具有改善的物理化学特性（包括改善的溶解度）的ZN-e4。在一项面对面的临床前研究中，与奥希替尼相比，ZN-e4在48小时内显示出450倍以上的溶解度。	230531	pj	D0222	新增药物	SXZ
BPI-15086													BPI-15086是贝达药业自主研发的、全新第三代突变选择性EGFR激酶抑制剂，已有的临床数据提示其在T790M突变的NSCLC患者上显示出了疗效，且安全性较好。临床前研究结果表示，其体内外生物学活性一致，作用机理明确，抗肿瘤效果显著，对于EGFR T790M耐药突变或敏感突变的非小细胞肺癌（NSCLC）尤为敏感。BPI-15086在体内有良好的药代-药效关系，且体内外药代动力学性质良好，药物蓄积或药物相互作用的风险较小。BPI-15086毒性相对较低，毒性反应可逆，且可测可控。	230531	pj	D0223	新增药物	SXZ
JBJ-09-063													JBJ-09-063是在JBJ-04-125-02的基础上进行改造的更有效的 EGFR变构抑制剂。临床前研究表明，相比于JBJ-04-125-02和奥希替尼，JBJ-09-063对EGFR L858R/T790M和EGFR L858R/T790M/C797S的抑制作用更强，且不受C797S突变的影响。	230531	pj	D0224	新增药物	SXZ
BI-4020													BI-4020由Boehringer Ingelheim公司研发。临床前研究显示：BI-4020能有效抑制T790M和/或C797S突变，并在含顺式三突变Del19/T790M/C797S的小鼠异体移植模型中显示出良好的药效。	230531	pj	D0225	新增药物	SXZ
AZ7608													2019年AACR学术会议报告了AZ7608联合Erbitux治疗C797S突变的临床前研究结果。	230531	pj	D0226	新增药物	SXZ
Patritumab Deruxtecan|U3-1402													Patritumab Deruxtecan(U3-1402)由日本第一三共株式会社研发的靶向HER3的抗体偶联类药物（ADC），主要由作用于HER3抗体Patritumab和细胞毒药物DX-8951（依喜替康）组成。I期临床研究纳入30名EGFR突变的晚期NSCLC患者。结果显示，U3-1402总体疾病控制率超过95%，特别是对脑转移患者的疾病控制率达到85.7%。U3-1402对EGFR -TKIs不同耐药机制的患者都有效，如EGFR C797S突变、MET扩增、HER2突变、BRAF和PIK3CA突变。	230531	pj	D0227	新增药物	SXZ
BBT-176													BBT-176是由BridgeBiotherapeutics公司开发的针对包括C797S在内的三重突变(Del19/T790M/C797S和L858R/T790M/C797S)的四代靶向药。临床前研究显示：BBT-176具有较强的抗肿瘤活性，特别是在动物模型中显示出明显的脑转移疗效。目前正在开展I/II期临床实验(NCT04820023)以观察BBT-176的安全性、耐受性和疗效。	230531	pj	D0228	新增药物	SXZ
QLH11811													QLH11811由齐鲁制药研发，对因EGFR C797S突变而导致奥希替尼耐药的NSCLC具有活性。临床前研究显示，QLH11811在野生型EGFR、激活突变ex19del以及多种组合型耐药突变中的活性均优于奥希替尼，并且针对L858R/C797S组合突变活性最高，在7种耐奥希替尼PDO模型显示了良好的抑制活性。	230531	pj	D0229	新增药物	SXZ
BPI-361175													BPI-361175由贝达药业研发，主要治疗携带EGFR C797S突变及其他EGFR相关突变的晚期NSCLC等实体瘤。临床前数据显示：BPI-361175能有效抑制携带EGFR C797S突变肿瘤细胞的增殖，并在多个携带EGFR相关突变的移植瘤模型上展现了良好的抗肿瘤作用。目前也正在开展I期临床试验。	230531	pj	D0230	新增药物	SXZ
BLU-701													BLU-701由BlueprintMedicines公司研发，和BLU-945互为补充，对BLU-945抑制活性不强的单突变及双突变EGFR具有较强活性，特别是在临床前研究显示出显著的中枢神经系统渗透能力。目前正在开展I期临床试验(NCT05153408)。	230531	pj	D0231	新增药物	SXZ
DAJH-1050766													DAJH-1050766是由成都地奥九泓药业研发的一款国研四代靶向药，结构上同二代ALK抑制剂布加替尼和四代EGFR抑制剂BPI-361175的结构具有一定的相似性，可用于治疗EGFR/ALK双突变的患者。目前正在开展DAJH-1050766片在晚期NSCLC患者中的安全性、耐受性、药代动力学特征及有效性的剂量递增、开放的I/II期临床研究。	230531	pj	D0232	新增药物	SXZ
ES-072													ES-072由浙江博生医药自主研发，治疗靶点为EGFR 19Del或L858R/T790M/C797S突变。临床前研究表明：ES-072不仅能克服使用第一代EGFR抑制剂后产生的T790M耐药突变，而且对服用第三代EGFR抑制剂奥希替尼后产生C797S突变也有治疗效果。目前正在开展I期临床试验。	230531	pj	D0233	新增药物	SXZ
H002													H002是由红云生物自主研发的国研药物。临床前研究显示：H002对具有EGFR Del19或L858R/T790M/C797S突变的多类肿瘤均有显著抑制效果。目前正在开展I/IIa期临床研究。	230531	pj	D0234	新增药物	SXZ
WJ13404													WJ13404由苏州君境生物研发，临床前研究显示该药对包括EGFR Del19/T790M/C797S和L858R/T790M/C797S在内的对第三代EGFR抑制剂不敏感的获得性EGFR变异都有很好的抑制活性，同时对野生型EGFR具有高度选择性。	230531	pj	D0235	新增药物	SXZ
Olmutinib|BI1482694|HM61713													Olmutinib (BI1482694/HM61713)是靶向T790M突变的第三代EGFR抑制剂。2016年5月17日，勃林格殷格翰宣布韩国制药企业韩美研发的Olmutinib已在韩国获得批准，用于既往接受过TKI治疗的局部晚期或转移性EGFR T790M突变NSCLC患者，这也是韩国批准的第一个治疗T790M突变的肺癌靶向药物。FDA在2015年12月21日授予了Olmutinib突破性药物资格。	230531	pj	D0236	新增药物	SXZ