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有机化学
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有机化学 ›› 2011, Vol. 31 ›› Issue (10): 1595-1595. 上一篇    下一篇

综述与进展

蛋白酪氨酸激酶小分子抑制剂的研究新进展

王勇，龙亚秋*   

  1. (中国科学院上海药物研究所新药研究国家重点实验室 上海 201203)
  • 收稿日期:2010-12-29 修回日期:2011-02-28 发布日期:2011-03-28
  • 通讯作者: 龙亚秋 E-mail:yqlong@mail.shcnc.ac.cn

Advances in Small-Molecule Inhibitors of Protein Tyrosine Kinases

WANG Yong, LONG Ya-Qiu   

  1. (State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sci-ences, Shanghai 201203)
  • Received:2010-12-29 Revised:2011-02-28 Published:2011-03-28

PDF

5246

被引次数

98 | 8

酪氨酸激酶在细胞的恶性生长和增殖中起着非常重要的作用, 发展选择性的蛋白激酶抑制剂来阻断或调控由于这些信号通路异常产生的疾病已被广泛认为是抗肿瘤药物开发的一个富有前景和有效的研究策略. 近年来科学家在蛋白酪氨酸激酶抑制剂这一领域进行了大量的工作, 合成了数百个受体型或者非受体型酪氨酸激酶抑制剂, 其中8个小分子抑制剂被美国食品药品管理局(FDA)批准作为抗肿瘤药物进入临床使用. 随着肿瘤多重耐药性的出现, 新机理的小分子酪氨酸激酶抑制剂被不断探索. 以小分子抑制剂与酪氨酸激酶不同的作用模式来进行分类, 系统地阐述了小分子酪氨酸激酶抑制剂的研究进展和发展趋势, 并对代表性化合物的合成进行了介绍.

关键词: 酪氨酸激酶, 抑制剂, 肿瘤, DFG motif (天冬氨酸-苯丙氨酸-甘氨酸模段), 分子靶向药物

Protein tyrosine kinases (PTKs) play a pivotal role in the signal transduction pathways, and their deregulation is highly related with the oncology including bladder, breast, colon, and lung cancers. Com-pounds that inhibit the kinase activity of PTKs are potential chemotherapeutics to treat tumors. With the emergence of the multiple drug resistance of tumor cells against the existing PTK inhibitors, new mechanism PTK inhibitors are designed and developed. This review is focused on the recent advance of the discovery and development of the small molecular PTK inhibitors, categorized according to the mode of ac-tion. Furthermore, the synthesis of the typical structures is described.

Key words: tyrosine kinases, inhibitors, cancer, DFG motif, molecular targeted therapy