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.
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).
