B-Raf激酶抑制剂的研究进展  

Advances in the research and development of B-Raf inhibitors

作　　者：董高超 周湘[1] 唐伟方[1] 陆涛[1] 

机构地区：[1]中国药科大学有机化学教研室,南京210009

出　　处：《中国药科大学学报》2014年第1期1-9,共9页Journal of China Pharmaceutical University

基　　金：中央高校基本科研业务费专项基金资助项目(No.JKQ2009013;JKZ2011005)~~

摘　　要：原癌基因B-Raf存在于多种肿瘤细胞中,尤其在黑色素瘤和甲状腺癌中。选择性B-Raf激酶抑制剂vemurafenib的上市引起了人们对此类抑制剂的广泛关注。通过分析vemurafenib与B-Raf激酶的结合模式,人们对B-Raf激酶抑制剂提出了新的分类。依据此分类,本文对蛋白质晶体数据库(PDB)出现的B-Raf激酶抑制剂进行了分析,比较每种类型抑制剂的作用模式,分析其构效关系,并对Raf激酶抑制剂的未来进行了展望。Oncogenic B-Raf has been identified in a variety of cancers with high incidence, especially in malignant melanoma and thyroid cancer. In 2011, selective B-Raf kinase inhibitor vemurafenib was approved by FDA, and that stimulated increasing interest in B-Raf inhibitors as anticancer agents. Through analyzing the X-ray crystal structure of vemurafenib bound to B-Raf kinase, new classification of B-Raf kinase inhibitors was proposed. This review focuses on diverse small-molecule inhibitors of B-Raf kinase published in protein data bank（PDB）from 2011 to date based on the new classification. The binding modes and structure-activity relationship（SAR）as well as the future development of these inhibitors are discussed.

关 键 词：B-Raf激酶 B-Raf激酶抑制剂 分类 

分 类 号：R914[医药卫生—药物化学]