Expanding the horizons of targeted protein degradation:A non-small molecule perspective  

作　　者：Xiaowei Huang Fengbo Wu Jing Ye Lian Wang Xiaoyun Wang Xiang Li Gu He 

机构地区：[1]Department of Pharmacy and Department of Dermatology&Venerology,West China Hospital,Sichuan University,Chengdu 610041,China [2]Department of Urology,West China Hospital,Sichuan University,Chengdu 610041,China [3]Laboratory of Dermatology,Clinical Institute of Inflammation and Immunology,Frontiers Science Center for Disease-Related Molecular Network and State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第6期2402-2427,共26页药学学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(22177084,82273559,82103757 and 82073473);the China Postdoctoral Science Foundation(2022M722283);PostDoctor Research Project,West China Hospital,Sichuan University(2023HXBH076,China);Sichuan Natural Science Foundation Project(2023NSFSC1554,China);the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21036,China).

摘　　要：Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond degradation.Non-small-molecule-based approaches play an irreplaceable role in this field.A wide variety of agents spanning a broad chemical spectrum,including peptides,nucleic acids,antibodies,and even vaccines,which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing paradigms.Herein we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs,including three major trajectories,to provide insights for the design strategies based on novel paradigms.

关 键 词：Targeted protein degradation Proteolysis targeting chimera ENDOCYTOSIS Autophagy Proximity-inducing modality Post-translational modification 

分 类 号：R914[医药卫生—药物化学]