摘要
包括肿瘤在内的许多疾病都是由特定的致病蛋白积累引起,降解致病蛋白或阻断致病蛋白活性,可抑制肿瘤的发生。但很多致病蛋白缺乏酶活性或缺乏药物作用的结合位点,致使很多小分子药物对肿瘤无能为力。以CR8为代表的分子胶降解剂是一类能够捕获这些“不可成药”蛋白并将其迅速降解清除的蛋白降解靶向嵌合体(PROTAC)。基于PROTAC技术诱导靶蛋白降解的策略,成为新药开发的研究热点。本文概述了PROTAC分子的结构特点及其在蛋白降解过程的作用,并根据作用靶点的不同,对基于PROTAC技术的分子胶降解剂的研究进展进行了综述,期望为新型分子胶降解剂的研究提供参考。
Many diseases,including tumors,are caused by the accumulation of specific pathogenic proteins,and the occurrence of tumors can be inhibited by degrading pathogenic proteins or blocking the activity of pathogenic proteins.However,many pathogenic proteins lack enzyme activity or binding sites for drug action,which makes many small molecule drugs powerless against tumors.Molecular glue degraders represented by CR8 are a class of PROTAC that can capture these"non-drug"proteins and quickly degrade and remove them.The strategy of inducing the degradation of target protein based on PROTAC technology has become a research hotspot of new drug development.In this paper,the structural characteristics of PROTAC molecule and its role in protein degradation process were summarized,and the recent research progress of molecular glue degraders based on PROTAC technology was reviewed according to the different targets,hoping to provide reference for the research of new molecular glue degraders.
作者
魏一飞
欧阳毅翔
程齐来
郭小华
WEI Yi-fei;OU YANG Yi-xiang;CHENG Qi-lai;GUO Xiao-hua(Pharmacy College,Gannan Medical University;Library of Gannan Medical University,Ganzhou,Jiangxi 341000)
出处
《赣南医学院学报》
2022年第11期1202-1208,共7页
JOURNAL OF GANNAN MEDICAL UNIVERSITY
基金
国家自然科学基金资助项目(22261004)
江西省自然科学基金资助项目(20202BAB206080)
江西省教育厅科学技术研究项目(GJJ201524)
江西省卫生计划生育委员会中医药科研项目(2017A246)。
关键词
蛋白降解靶向嵌合体
分子胶降解剂
蛋白降解
泛素化
Proteolysis targeting chimera
Molecular glue degraders
Protein degradation
Ubiquitin
