HSP90小分子抑制剂研究进展  

Progress in the study of small molecule inhibitors of HSP90

作　　者：任景[1] 严碧波[2] 石峰[1] 熊兵[1] 沈竞康[1] 

机构地区：[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 [2]长江大学电信学院,湖北荆州434023

出　　处：《药学学报》2015年第6期640-649,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81273368,81330076);国家“新药创制”科技重大专项资助项目(2014ZX09507-002)

摘　　要：HSP90既是细胞应激反应的生物标志物,也是细胞内重要的分子伴侣蛋白。HSP90调控的很多客户蛋白,如EGFR、Met、Raf-1、IKK、p53等,均与肿瘤等疾病的发生和发展关系密切。HSP90抑制剂通过与靶点结合抑制其活性,导致其客户蛋白无法正确折叠而降解,可从多环节多途径影响细胞生物学效应,因此HSP90抑制剂在肿瘤治疗等领域展示出良好应用前景。本文将对近年来重要的小分子HSP90-N端抑制剂的研究进展进行综述。HSP90, which is the biomarker of cell stress and endogenous protective protein, functions as a molecular chaperone. Many client proteins of HSP90, including EGFR, Met, Raf-1, IKK and p53, play important roles in the occurrence and development of tumor. Binding of HSP90 inhibitors triggers the deactivation of HSP90, resulting in client protein degradation, and hence inhibits the tumor growth by blocking multiple targets involved in signaling of tumor proliferation. This review summarizes recent development of small molecule inhibitors bound to N-terminal of HSP90.

关 键 词：HSP90 客户蛋白 肿瘤 抑制剂 

分 类 号：R916[医药卫生—药学]