基于蛋白降解靶向嵌合体(PROTAC)的药物研发新模式  

A novel model for drug discovery based on proteolysis-targeting chimeras(PROTAC)

作　　者：李炳坤 杨宁 李鹏运 郑志兵 LI Bing-kun;YANG Ning;LI Peng-yun;ZHENG Zhi-bing(National Engineering Research Center for Strategic Drugs,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]军事科学院军事医学研究院毒物药物研究所,国家应急防控药物工程技术研究中心,北京100850

出　　处：《军事医学》2023年第1期1-12,共12页Military Medical Sciences

摘　　要：蛋白降解靶向嵌合体(PROTAC)是一种利用泛素-蛋白酶体系统对靶蛋白进行降解的双功能分子。近年来,PROTAC技术广泛应用于肿瘤、自身免疫疾病、神经退行性疾病及病毒感染的治疗,成为新一代药物研发的热点。该文综述了该领域发展的重要里程碑事件和近年的重要研究进展,阐释了PROTAC的设计理念,并讨论了PROTAC靶向降解的挑战及未来发展方向。Proteolysis-targeting chimeras(PROTAC)is a bifunctional molecule that targets protein of interest(POI)for degradation by co-opting the ubiquitin-proteasome system(UPS).In recent years,PROTAC technology has been widely explored as a novel therapeutic strategy for cancer,autoimmune diseases,neurodegenerative diseases and viral infection,which has become a hot spot and priority for drug development.This review is intended to outline the important milestones and the key research progress in the field of PROTAC,offer recommendations on the design of PROTAC,and describe the challenges to and prospects of targeted degradation by PROTAC.

关 键 词：蛋白降解靶向嵌合体 靶蛋白 E3泛素连接酶 降解剂 

分 类 号：R918[医药卫生—药学] R945