Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China; School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
Eur J Med Chem. 2024 Sep 5;275:116562. doi: 10.1016/j.ejmech.2024.116562. Epub 2024 Jun 3.
As a molecular chaperone, heat shock protein 90 (HSP90) plays important roles in the folding, stabilization, activation, and degradation of over 500 client proteins, and is extensively involved in cell signaling, proliferation, and survival. Thus, it has emerged as an important target in a variety of diseases, including cancer, neurodegenerative diseases, and viral infections. Therefore, targeted inhibition of HSP90 provides a valuable and promising therapeutic strategy for the treatment of HSP90-related diseases. This review aims to systematically summarize the progress of research on HSP90 inhibitors in the last five years, focusing on their structural features, design strategies, and biological activities. It will refer to the natural products and their derivatives (including novobiocin derivatives, deguelin derivatives, quinone derivatives, and terpenoid derivatives), and to synthetic small molecules (including resorcinol derivatives, pyrazoles derivatives, triazole derivatives, pyrimidine derivatives, benzamide derivatives, benzothiazole derivatives, and benzofuran derivatives). In addition, the major HSP90 small-molecule inhibitors that have moved into clinical trials to date are also presented here.
作为分子伴侣，热休克蛋白 90（HSP90）在超过 500 种客户蛋白的折叠、稳定、激活和降解中发挥着重要作用，并广泛参与细胞信号转导、增殖和存活。因此，它已成为包括癌症、神经退行性疾病和病毒感染在内的多种疾病的重要靶点。因此，靶向抑制 HSP90 为治疗 HSP90 相关疾病提供了有价值且有前途的治疗策略。本综述旨在系统总结过去五年 HSP90 抑制剂的研究进展，重点关注其结构特征、设计策略和生物学活性。它将参考天然产物及其衍生物（包括新生霉素衍生物、蜕皮甾酮衍生物、醌衍生物和萜类衍生物）以及合成小分子（包括间苯二酚衍生物、吡唑衍生物、三唑衍生物、嘧啶衍生物、苯甲酰胺衍生物、苯并噻唑衍生物和苯并呋喃衍生物）。此外，还介绍了迄今为止进入临床试验的主要 HSP90 小分子抑制剂。
