基于靶向蛋白降解技术的药物研究进展

Research Progress on Protac-induced Targeted Protein Degradation for Drug Discovery

靶向蛋白降解技术(PROTAC)是一种利用双功能小分子,使部分不能与E3泛素连接酶结合的靶蛋白泛素化,进而经泛素-蛋白酶体途径降解的新技术。PROTAC技术的效果优于传统抑制剂,还可避免耐药性问题。详细介绍了PROTAC技术的作用机制,发展历程以及优势。并对该技术在药物研发领域面临的挑战进行了展望。

Bifunctional small molecules were adopted by proteolysis targeting chimera(PROTAC)method,to bind a target protein and an ubiquitin E3ligase simultaneously,thus causing ubiquitination and degradation of the target protein.PROTAC exhibited better effects than traditional inhibitors and overcomed drug resistance in cancer therapy.The mechanisms,recent progress and advantages were reviewed particularly.Furthermore,the challenges and future direction of the PROTAC were prospected.