BMS-908662 | 1029873-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: BMS-908662
• 英文别名: methyl {5-[2-(5-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate；Methyl (5-(2-(5-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl)carbamate；methyl N-[6-[2-(5-chloro-2-methylphenyl)-1-hydroxy-3-oxoisoindol-1-yl]-1H-benzimidazol-2-yl]carbamate
• CAS: 1029873-02-6；870603-16-0
• 化学式: C₂₄H₁₉ClN₄O₄
• 分子量: 462.892
• InChiKey: MMNNTJYFHUDSKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

文献信息

• Raf Modulators and Methods of Use
  申请人：Anand Kumar Neel

  公开号：US20080009488A1

  公开（公告）日：2008-01-10

  The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly Raf. Methods of using the compounds and pharmaceutical compositions thereof to treat kinase-dependent diseases and conditions are also an aspect of the invention.

  本发明提供了用于调节蛋白激酶酶活性以调节细胞活动，如增殖、分化、程序性细胞死亡、迁移和化学侵袭的化合物。本发明的化合物抑制、调节和/或调节激酶，特别是Raf。使用这些化合物和制药组合物来治疗激酶依赖性疾病和病症的方法也是本发明的一个方面。
• Raf Modulators And Methods Of Use
  申请人：Anand Neel Kumar

  公开号：US20110071145A1

  公开（公告）日：2011-03-24

  The present invention relates to compounds of the Formula I, wherein G, A, X1, X2, X3, Z, E, Y, and X are defined herein. The compounds modulate protein kinase enzymatic activity to modulate cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly Raf. Methods of using and preparing the compounds, and pharmaceutical compositions thereof, to treat kinase-dependent diseases and conditions are also an aspect of the invention.

  本发明涉及式I的化合物，其中G，A，X1，X2，X3，Z，E，Y和X在此定义。该化合物调节蛋白激酶酶活性，以调节细胞活动，如增殖，分化，程序性细胞死亡，迁移和化学侵袭。该发明的化合物抑制，调节和/或调节激酶，特别是Raf。使用和制备该化合物的方法以及其药物组成物，用于治疗激酶依赖性疾病和病况也是本发明的一个方面。
• ERK1 and ERK2 mutations that confer resistance to MAPK pathway inhibitors
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US11186874B2

  公开（公告）日：2021-11-30

  Isolated mutant ERK polypeptides and nucleic acids encoding the mutant ERK polypeptides are provided. Methods of screening cancer-containing samples for an ERK polypeptide mutation that confers resistance to treatment with a first MAPK pathway inhibitor are provided. Methods of optimizing treatment of a subject having cancer and methods of identifying compounds useful in treating cancer are also provided.

  提供了分离的突变型ERK多肽及其编码的核酸。介绍了在含有癌症的样本中筛选赋予对首个MAPK通路抑制剂治疗产生抗性的ERK多肽突变的方法。还提供了优化癌症患者治疗方法以及识别可用于治疗癌症化合物的方法。
• Methods of treating resistant cancers
  申请人：University of Maryland, Baltimore

  公开号：US11246856B2

  公开（公告）日：2022-02-15

  Provided herein is a method for reducing resistance in an individual having a drug resistant cancer, for example, a BRAF inhibitor resistant cancer. A Hippo signaling pathway inhibitor such as a Yes-associated protein 1 (YAP1) inhibitor, a Transcriptional Coactivator with PDZ-binding motif (TAZ) inhibitor, a Transcription enhancer domain (TEAD) inhibitor or a combination of these is administered. Also provided is a method of treating BRAF inhibitor resistance in an individual with a BRAF inhibitor resistant cancer, for example, malignant melanoma, with a Hippo signaling pathway inhibitor, such as Verteporfin, and a BRAF inhibitor.

  本文提供了一种降低耐药性癌症（例如对 BRAF 抑制剂耐药的癌症）患者耐药性的方法。施用希波信号通路抑制剂，如是相关蛋白 1（YAP1）抑制剂、具有 PDZ 结合基调的转录激活子（TAZ）抑制剂、转录增强子结构域（TEAD）抑制剂或这些抑制剂的组合。还提供了一种治疗 BRAF 抑制剂耐药性癌症（例如恶性黑色素瘤）患者的 BRAF 抑制剂耐药性的方法，使用 Hippo 信号通路抑制剂（例如 Verteporfin）和 BRAF 抑制剂。
• IDENTIFICATION OF DRUGS TARGETING NON-GENETIC DRUG TOLERANCE PROGRAMS IN CANCER
  申请人：ETH Zurich

  公开号：EP3559276A1

  公开（公告）日：2019-10-30