hsp90 小分子抑制剂研究进展progress in the study of - 药学学报.pdf

640 药学学报 Acta Pharmaceutica Sinica 20 15, 50 (6): 640 649 HSP90 分子抑制剂研究进展 1† 2† 1 1 1* 景 , 严碧波 , 石 峰 , 熊 兵 , 沈竞康 (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 20 1203; 2. 长江大学电信学院, 湖北 荆州 434023) 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 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。 关键词: HSP90; 客户蛋白; 肿瘤; 抑制剂 中图分类号: R9 16 文献标识码: A 文章编号: 0513-4870 (20 15) 06-0640-10 Progress in the study of small molecule inhibitors of HSP90 1† 2† 1 1 1* REN Jing , YAN Bi-bo , SHI Feng , XIONG Bing , SHEN Jing-kang (1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Ac ademy of Sciences, Shanghai 201203, China; 2. College of Electronics and Inf ormation, Yangtze University, Jingzhou 434023, China ) Abstract : 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 inhibitor