Department of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Wenhua Road No. 103, Shenyang 110016, China.
School of Life Science and Medicine, Dalian University of Technology, Dagong Road No. 2, Panjin, 124221, China.
Curr Drug Targets. 2020;21(3):302-317. doi: 10.2174/1389450120666190829162544.
HSP90 is a member of the family of heat shock proteins responsible for folding proteins into mature conformations and thus maintaining their biological function in cells. Since it is involved in all hallmarks of cancer, HSP90 has been considered as a promising drug target for cancer therapy. Eighteen HSP90 inhibitors have entered clinical trials, however, none has been approved by the FDA. There is still a great need for novel HSP90 inhibitors with strong anticancer activity and good safety profile. In the past several years, many new molecules were identified as HSP90 inhibitors and some of them have shown promising pharmacological profiles in preclinical evaluations. In this review, HSP90 inhibitors identified from 2014 to date are summarized and their design strategies, chemical structures, and biological activities are reviewed. The inhibitors are categorized by their different target domains and selectivity as N-terminal, C-terminal, and isoform-selective HSP90 inhibitors.
HSP90 是热休克蛋白家族的一员，负责将蛋白质折叠成成熟的构象，从而维持其在细胞中的生物功能。由于 HSP90 参与了癌症的所有特征，因此它被认为是癌症治疗的一个有前途的药物靶点。已经有 18 种 HSP90 抑制剂进入临床试验，但没有一种被 FDA 批准。仍然需要具有强大抗癌活性和良好安全性的新型 HSP90 抑制剂。在过去的几年中，已经鉴定出许多新的 HSP90 抑制剂，其中一些在临床前评估中显示出了有前景的药理学特征。在这篇综述中，总结了 2014 年以来发现的 HSP90 抑制剂，并对其设计策略、化学结构和生物学活性进行了综述。抑制剂根据其不同的靶结构域和选择性分为 N 端、C 端和亚型选择性 HSP90 抑制剂。
