Advances and prospects in targeted protein degradation
10.12206/j.issn.2097-2024.202303008
- VernacularTitle:靶向蛋白降解技术研究进展与展望
- Author:
Luozhu ZHOU
1
;
Chunquan SHENG
1
Author Information
1. Department of Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
- Publication Type:Reviews
- Keywords:
targeted protein degradation;
ubiquitin–proteasome system;
lysosomal degradation pathway;
drug discovery;
PROTAC
- From:
Journal of Pharmaceutical Practice
2023;41(6):341-351
- CountryChina
- Language:Chinese
-
Abstract:
Targeted protein degradation (TPD) techniques eliminate pathogenic proteins by hijacking the intracellular proteolysis machinery which includes the ubiquitin-proteasome system (UPS) and the lysosomal degradation pathway, holding promise to overcome the limitations of traditional inhibitors and further broaden the target space including many “undruggable” targets, and provide new targeted treatments for drug discovery. In this review, recent advances in a variety of promising TPD strategies were summarized, such as proteolysis targeting chimera (PROTAC), molecular glue, lysosome-targeting chimaera (LYTAC), autophagosome-tethering compound (ATTEC), autophagy-targeting chimera AUTAC and AUTOTAC, particularly. The representative case studies, potential applications and challenges were analyzed.
