热休克蛋白90 抑制剂的研究进展progress in the study of - 药学学报.pdf

药学学报 Acta Pharmaceutica Sinica 2010, 45 (7) : 8 13820 ·813 · 热休克蛋白90 抑制剂的研究进展 罗浩铭, 孙 薇, 尹建元, 杨晓虹* (吉林大学药学院, 吉林 长春 130021) 摘要: 热休克蛋白 90 (Hsp90) 是抗肿瘤 物作用的新靶点, 其抑制剂通过破坏体内蛋白的结构和降解过程 起到抗肿瘤的作用。近年来, Hsp90 抑制剂的研究不仅拘泥于对天然产物的结构改造, 更多的是通过高通量筛选 和计算机辅助 物设计方法进行先导化合物的发现以及合成新型结构的Hsp90 抑制剂。Hsp90 作为一类重要的 生物学靶点在抗肿瘤 物的研制过程中越来越 到重视。本文对近年来以Hsp90 为靶点的小分子抑制剂的研究 进展进行综述。 关键词: 热休克蛋白90 抑制剂; 高通量筛选; 构效关系; 分子-蛋白复合物; 进展 中图分类号: R916 文献标识码:A 文章编号: 05 13-4870 (2010) 07-0813-08 Progress in the study of heat shock protein 90 inhibitors * LUO Hao-ming, SUN Wei, YIN Jian-yuan, YANG Xiao-hong (School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China) Abstract: Heat shock protein 90 is a new target of antitumor drug, the inhibitor of Hsp90 fight against tumor by destroy and degrade the structure of protein. In recent years, looking for Hsp90 inhibitor is not only via structure modifying of natural products, but also via high throughput screening and computer aided drug design to find and synthesize new kinds of Hsp90 inhibitor. Anyway, Hsp90 inhibitor has considered as an important biology target and to pay more and more attention. This review describes recent developments of small molecule Hsp90 inhibitors. Key words: heat shock protein 90 inhibitor; high throughput screening; structure activity relationship; molecule-protein complex; progress 热休克蛋白 (Hsp90) 大量存在于真核细胞中, Hsp90 与Hsp70 通过第三方伴侣蛋白Hop 连接成为 是一类ATP 依赖的分子伴侣, 在维持构型稳定、保持 分子伴侣复合物,