Emerging hsp90 inhibitors: From discovery to clinic
Emerging hsp90 inhibitors: From discovery to clinic
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DOI：
10.2174/187152006774755483
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发表时间：
2006-01-01
影响因子：
2.8
通讯作者：
Moulick, K.
中科院分区：
文献类型：
--
作者：
Chiosis, G.;Rodina, A.;Moulick, K.
HSP90是一种伴侣蛋白，在维持癌细胞转化和提高癌细胞的存活和生长潜能方面具有重要作用。Hsp90蛋白客户介导的信号通路的激活对细胞增殖、细胞周期进程和细胞凋亡的调控是必要的。此外，负责转化的功能获得突变通常需要Hsp90来维持其折叠的、功能活跃的构象。这些特性使Hsp90有望成为癌症治疗的重要靶点，并促进伴侣蛋白小分子抑制物的识别、开发和临床翻译。这篇综述旨在更新读者关于几种现有的和正在出现的Hsp90 ATPase活性的直接抑制剂的状况。
Hsp90 is a chaperone with important roles in maintaining transformation and in elevating the survival and growth potential of cancer cells. Activation of signaling pathways mediated by Hsp90 protein clients is necessary for cell proliferation, regulation of cell cycle progression and apoptosis. Additionally, gain-of-function mutations responsible for transformation often require Hsp90 for the maintenance of their folded, functionally active conformations. These characteristics promise Hsp90 as an important target in cancer therapy and prompt for the identification, development and clinical translation of small molecule inhibitors of the chaperone. This review intends to update the reader on the status of several existing and emerging classes of direct inhibitors of Hsp90 ATPase activity.