热休克蛋白70小分子抑制剂的研究进展  

Current status and perspectives of small molecule inhibitors of heat shock protein 70

作　　者：朱金言 何明慧 吴凡 余荧蓝 罗雷[1] 邵豪 ZHU Jin-yan;HE Ming-hui;WU Fan;YU Ying-lan;LUO Lei;SHAO Hao(College of Pharmaceutical Sciences,Southwest University,Chongqing 400715,China)

机构地区：[1]西南大学药学院.中医药学院,重庆400715

出　　处：《药学学报》2024年第11期2962-2974,共13页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金青年科学基金(82104001);中央高校基本科研业务费专项资金项目(5330501000,5330501059)。

摘　　要：热休克蛋白70(heat shock protein 70,Hsp70)是一类细胞中广泛存在的分子伴侣,具有维持细胞内蛋白质稳态的功能。Hsp70在多种疾病的发生发展中也发挥了重要的作用,包括癌症、神经退行性疾病和传染性疾病等,是治疗这些疾病的潜在靶点,因此有必要开发小分子抑制剂对这一重要靶点进行验证。近年来针对Hsp70小分子抑制剂的研究取得了显著进展,通过不同方式抑制Hsp70功能的小分子化合物都有报道。本文简要介绍了Hsp70的结构域、共伴侣蛋白及相关的疾病,系统总结了其小分子抑制剂的发现过程及作用特点,以期为Hsp70小分子抑制剂的进一步研发提供参考。Heat shock protein 70(Hsp70)is a class of molecular chaperones essential for maintaining protein homeostasis in cells.Hsp70s also play important roles in the pathogenesis of a variety of diseases,including cancer,neurodegenerative diseases and infectious diseases,which makes them potential targets for the treatment of these diseases.It is necessary to develop small molecule inhibitors to validate this class of important therapeutic targets.In recent years,the discovery of small molecule inhibitors for Hsp70s has made remarkable progress,and Hsp70 inhibitors with different modalities have been reported.In this paper,Hsp70 and relevant diseases are briefly introduced,and the discovery of Hsp70 small molecule inhibitors with distinct modalities are summarized,providing reference for the further discovery and development of Hsp70 small molecule inhibitors.

关 键 词：热休克蛋白70 分子伴侣 小分子抑制剂 变构抑制剂 蛋白-蛋白相互作用 

分 类 号：R914[医药卫生—药物化学]