2. Academic Validation
  3. Targeted protein degradation: mechanisms, strategies and application

Targeted protein degradation: mechanisms, strategies and application

  • Signal Transduct Target Ther. 2022 Apr 4;7(1):113. doi: 10.1038/s41392-022-00966-4.
Lin Zhao # 1,  Jia Zhao # 1,  Kunhong Zhong # 2,  Aiping Tong 3,  Da Jia 4
Affiliations

Affiliations

  • 1 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, 610041, Chengdu, China.
  • 2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 610041, Chengdu, China.
  • 3 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 610041, Chengdu, China. aipingtong@scu.edu.cn.
  • 4 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, 610041, Chengdu, China. Jiada@scu.edu.cn.
  • # Contributed equally.
PMID: 35379777 DOI: 10.1038/s41392-022-00966-4
Abstract

Traditional drug discovery mainly focuses on direct regulation of protein activity. The development and application of protein activity modulators, particularly inhibitors, has been the mainstream in drug development. In recent years, PROteolysis TArgeting Chimeras (PROTAC) technology has emerged as one of the most promising approaches to remove specific disease-associated proteins by exploiting cells' own destruction machinery. In addition to PROTAC, many different targeted protein degradation (TPD) strategies including, but not limited to, molecular glue, Lysosome-Targeting Chimaera (LYTAC), and Antibody-based PROTAC (AbTAC), are emerging. These technologies have not only greatly expanded the scope of TPD, but also provided fresh insights into drug discovery. Here, we summarize recent advances of major TPD technologies, discuss their potential applications, and hope to provide a prime for both biologists and chemists who are interested in this vibrant field.

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