蛋白降解靶向嵌合体药物研究新进展OA

Proteolysis-targeting chimeras(PROTACs)are heterobifunctional molecules composed of an E3 ubiquitin ligase ligand,a linker,and a protein of interest(POI)ligand.They function by recruiting intracellular E3 ubiquitin ligases to spe-cifically ubiquitinate the POI,thereby directing the proteasome to recognize and degrade the POI,achieving precise degradation of the POI.Compared with conventional small-molecule inhibitors,PROTACs have advantages such as the ability to target"undrug-gable"proteins,prolonged pharmacological effects,and the potential to overcome drug resistance.To date,a number of PROTACs have progressed to the clinical research stage,showing promising therapeutic potential in oncology and immunology.This review summarizes the mechanisms of action,unique advantages,current research status and recent progress of PROTACs,aiming to pro-vide insights for the future research and development of PROTAC drugs.