4-(benzenesulfonyl)-N-[(5-chloro-1-benzothiophen-3-yl)methyl]thiophene-2-sulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 4-(benzenesulfonyl)-N-[(5-chloro-1-benzothiophen-3-yl)methyl]thiophene-2-sulfonamide
• 化学式: C₁₉H₁₄ClNO₄S₄
• 分子量: 484.0
• InChiKey: MMMCHQRHQOEXDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  154
• 氢给体数：
  1
• 氢受体数：
  7

文献信息

• Inhibitors of GRB2-associated binding protein 1 (GAB1) and methods of treating cancer using the same
  申请人：Arizona Board of Regents on Behalf of University of Arizona

  公开号：US10448637B2

  公开（公告）日：2019-10-22

  Identification and evaluation of a set of first-in-class potent inhibitors targeting a new cancer target, Grb2-associated binder˜1 (GAB1), which integrates signals from different signaling pathways and is frequently over-expressed in cancer ceils. Intensive computational modeling is utilized to understand the structure of the GAB1 pleckstrin homology (PH) domain and screened five million compounds. Upon biological evaluation, several inhibitors were found that induced large conformational changes of the target structure exhibited strong selective binding to GAB1 PH domain. Particularly, these inhibitors demonstrated potent and tumor-specific cytotoxicity in breast cancer cells. This targeting GAB1 signaling may be used for cancer therapy, especially for triple negative breast cancer patients.

  鉴定和评估一组针对癌症新靶点--Grb2-associated binder˜1 (GAB1)--的一流强效抑制剂，GAB1整合了来自不同信号通路的信号，在癌细胞中经常过度表达。为了了解 GAB1 pleckstrin homology（PH）结构域的结构，研究人员进行了大量的计算建模，并筛选了五百万种化合物。经过生物学评估，发现了几种能诱导目标结构发生巨大构象变化的抑制剂，它们与 GAB1 PH 结构域的结合具有很强的选择性。特别是，这些抑制剂对乳腺癌细胞具有强效的肿瘤特异性细胞毒性。这种靶向 GAB1 信号转导的方法可用于癌症治疗，尤其是三阴性乳腺癌患者。
• INHIBITORS OF GRB2-ASSOCIATED BINDING PROTEIN 1 (GAB1) AND METHODS OF TREATING CANCER USING THE SAME
  申请人：Arizona Board of Regents on Behalf of University of Arizona

  公开号：US20170311597A1

  公开（公告）日：2017-11-02

  Identification and evaluation of a set of first-in-class potent inhibitors targeting a new cancer target, Grb2-associated binder˜1 (GAB1), which integrates signals from different signaling pathways and is frequently over-expressed in cancer ceils. Intensive computational modeling is utilized to understand the structure of the GAB1 pleckstrin homology (PH) domain and screened five million compounds. Upon biological evaluation, several inhibitors were found that induced large conformational changes of the target structure exhibited strong selective binding to GAB1 PH domain. Particularly, these inhibitors demonstrated potent and tumor-specific cytotoxicity in breast cancer cells. This targeting GAB1 signaling may be used for cancer therapy, especially for triple negative breast cancer patients.
• Inhibitors for Treatment of Hematological Malignancies
  申请人：Masarykova Univerzita

  公开号：US20220000879A1

  公开（公告）日：2022-01-06

  A new approach to treatment of hematological malignancies. A GAB1 inhibitor for use in a method of treatment of a hematological malignancy is disclosed. The GAB1 inhibitor may be administered alone, or simultaneously or sequentially with a BTK inhibitor to achieve a synergistic effect.