Heat Shock Protein 90 Inhibitors: An Update on Achievements, Challenges, and Future Directions
Heat Shock Protein 90 Inhibitors: An Update on Achievements, Challenges, and Future Directions
复制标题
热休克蛋白 90 抑制剂：成就、挑战和未来方向的最新进展
DOI：
10.1021/acs.jmedchem.9b00940
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发表时间：
2020-03-12
影响因子：
7.3
通讯作者：
Xu, Xiao-Li
中科院分区：
文献类型：
--
作者：
Li, Li;Wang, Lei;Xu, Xiao-Li
Hsp90 is one of the most important chaperones involved in regulating the maturation of more than 300 client proteins, many of which are closely associated with refractory diseases, including cancer, neurodegenerative diseases, and viral infections. Clinical Hsp90 inhibitors bind to the ATP pocket in the N-terminal domain of Hsp90 and subsequently suppress the ATPase activity of Hsp90. Recently, with the increased understanding of the discrepancies in the isoforms of Hsp90 and the modes of Hsp90-co-chaperone-client complex interactions, some new strategies for Hsp90 inhibition have emerged. Novel Hsp90 inhibitors that offer selective suppression of Hsp90 isoforms or specific disruption of Hsp90-co-chaperone protein-protein interactions are expected to show with satisfactory efficacy and safety profiles. This review summarizes the recent progress in Hsp90 inhibitors. Additionally, Hsp90 inhibitory strategies are emphasized in this review.
