贝扎替尼 | 1357920-84-3

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 贝扎替尼
• 中文别名: ALK和TRKA、TRKB、TRKC双重抑制剂(BELIZATINIB)；4-氟-N-(6-((4-(2-羟基丙烷-2-基)哌啶-1-基)甲基)-1-(顺式-4-(异丙基氨甲酰)环己基)-1H-苯并[D]咪唑-2-基)苯甲酰胺；化合物BELIZATINIB
• 英文名称: (E)-4-fluoro-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide
• 英文别名: Belizatinib；4-fluoro-N-[6-[[4-(2-hydroxypropan-2-yl)piperidin-1-yl]methyl]-1-[4-(propan-2-ylcarbamoyl)cyclohexyl]benzimidazol-2-yl]benzamide
• CAS: 1357920-84-3
• 化学式: C₃₃H₄₄FN₅O₃
• 分子量: 577.742
• InChiKey: WSTUJEXAPHIEIM-UHFFFAOYSA-N

物化性质

• 密度：
  1.27±0.1 g/cm3(Predicted)
• 溶解度：
  DMF:30.0(最大浓度 mg/mL);51.93(最大浓度 mM)DMSO:143.33(最大浓度 mg/mL);248.08(最大浓度 mM)乙醇:65.0(最大浓度 mg/mL);112.5(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  99.5
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

Belizatinib (TSR-011) 是一种有效的 ALK（IC50=0.7 nM）和 tropomyosin receptor kinase (TRK) （IC50<3 nM）抑制剂。

靶点

Target	Value
TrkA	()
TrkB	()
TrkC	()

体外研究

TSR-011 对野生型重组 ALK 激酶活性具有高度亲和力，IC50 为 0.7 nM；同时它还能够有效抑制原肌球蛋白受体激酶（TRK）A、B 和 C（IC50 小于3 nM）。

体内研究

在小鼠模型中，TSR-011 能够对 ALK 依赖的肿瘤生长发挥有效的持久抑制作用，并且具有良好的耐受性。

反应信息

• 作为产物：
  描述：

  (3-氟-4-硝基苯基)甲醇 在 palladium 10% on activated carbon 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 37.75h， 生成 贝扎替尼
  参考文献：
  名称：

  [EN] BENZIMIDAZOLE AND AZABENZIMIDAZOLE COMPOUNDS THAT INHIBIT ANAPLASTIC LYMPHOMA KINASE
  [FR] COMPOSÉS BENZIMIDAZOLE ET AZABENZIMIDAZOLE QUI INHIBENT LA KINASE DES LYMPHOMES ANAPLASIQUES

  摘要：

  公式（I）的化合物是有用的间变性淋巴瘤激酶抑制剂。公式（I）的化合物具有以下结构：其中变量的定义如下。

  公开号：

  WO2012018668A1

文献信息

• BENZIMIDAZOLE AND AZABENZIMIDAZOLE COMPOUNDS THAT INHIBIT ANAPLASTIC LYMPHOMA KINASE
  申请人：Boezio Christiane M.

  公开号：US20130217668A1

  公开（公告）日：2013-08-22

  Compounds of Formula (I) are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula (I) have the following structure: where the definitions of the variables are provided herein.

  公式（I）的化合物是阿纳普拉斯腺瘤激酶的有用抑制剂。公式（I）的化合物具有以下结构：其中变量的定义在此提供。
• Point mutations in TRK inhibitor-resistant cancer and methods relating to the same
  申请人：Loxo Oncology, Inc.

  公开号：US10370727B2

  公开（公告）日：2019-08-06

  Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment for a subject having a cancer, methods of selecting a subject having a cancer for a treatment that does not include a Trk inhibitor, methods of determining the likelihood that a subject having a cancer will have a positive response to a treatment with a Trk inhibitor, methods of predicting the efficacy of a Trk inhibitor in a subject having cancer, methods of determining a subject's risk for developing a Trk inhibitor-resistant cancer, and methods of determining the presence of a Trk inhibitor-resistant cancer in a subject, based on the detection of a cell from a sample from the subject that has at least one of the the point mutations in NTRK1 and/or NTRK2 and/or NTRK3.

  本文提供了治疗癌症受试者的方法、为癌症受试者选择治疗方法的方法、为不包括Trk抑制剂的治疗方法选择癌症受试者的方法、确定癌症受试者对Trk抑制剂治疗产生阳性反应的可能性的方法、预测Trk抑制剂对癌症受试者疗效的方法、确定受试者罹患Trk抑制剂抗性癌症风险的方法，以及根据从受试者样本中检测到的细胞具有NTRK1和/或NTRK2和/或NTRK3中至少一种点突变，确定受试者存在Trk抑制剂抗性癌症的方法。
• Inhibitors of DUX4 induction for regulation of muscle function
  申请人：Sonic Master Limited

  公开号：US11065243B2

  公开（公告）日：2021-07-20

  Disclosed are methods and compositions for the treatment of facioscapulohumeral muscular dystrophy. In some cases, the methods and compositions involve the use of kinase inhibitors include Src, Syk, Abl, Tie, Flt, ErbB, Trk, PRKDC, and Yes families to repress DUX4 expression in muscle cells. Further disclosed are methods and cell based assays for screening compounds for the treatment of facioscapulohumeral muscular dystrophy.

  所公开的是治疗面肱骨肌营养不良症的方法和组合物。在某些情况下，这些方法和组合物涉及使用包括 Src、Syk、Abl、Tie、Flt、ErbB、Trk、PRKDC 和 Yes 家族在内的激酶抑制剂来抑制肌肉细胞中 DUX4 的表达。进一步公开了用于筛选治疗面肱骨肌营养不良症的化合物的方法和基于细胞的检测方法。
• POINT MUTATIONS IN TRK INHIBITOR-RESISTANT CANCER AND METHODS RELATING TO THE SAME
  申请人：Loxo Oncology, Inc.

  公开号：US20170260589A1

  公开（公告）日：2017-09-14

  Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment for a subject having a cancer, methods of selecting a subject having a cancer for a treatment that does not include a Trk inhibitor, methods of determining the likelihood that a subject having a cancer will have a positive response to a treatment with a Trk inhibitor, methods of predicting the efficacy of a Trk inhibitor in a subject having cancer, methods of determining a subject's risk for developing a Trk inhibitor-resistant cancer, and methods of determining the presence of a Trk inhibitor-resistant cancer in a subject, based on the detection of a cell from a sample from the subject that has at least one of the the point mutations in NTRK1 and/or NTRK2 and/or NTRK3.
• FORMULATIONS OF A MACROCYCLIC TRK KINASE INHIBITOR
  申请人：Array BioPharma Inc.

  公开号：US20190247398A1

  公开（公告）日：2019-08-15

  The present application in some embodiments provides a pharmaceutical composition comprising: and a compounding agent. Further provided herein are methods of making and methods of using the pharmaceutical compositions, for example, in the treatment of cancer.