Recent Advances of Degradation Technologies Based on PROTAC Mechanism

Mingchao Xiao; Jiaojiao Zhao; Qiang Wang; Jia Liu; Leina Ma

doi:10.3390/biom12091257

Recent Advances of Degradation Technologies Based on PROTAC Mechanism

Biomolecules. 2022 Sep 7;12(9):1257. doi: 10.3390/biom12091257.

Authors

Mingchao Xiao^{1

2}, Jiaojiao Zhao^{1

2}, Qiang Wang³, Jia Liu⁴, Leina Ma¹

Affiliations

¹ Cancer Institute of The Affiliated Hospital, Qingdao University, Qingdao 266071, China.
² School of Basic Medicine, Qingdao University, Qingdao 266071, China.
³ Oncology Department, Shandong Second Provincial General Hospital, Jinan 250022, China.
⁴ Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266071, China.

Abstract

PROTAC (proteolysis-targeting chimeras), which selectively degrades target proteins, has become the most popular technology for drug development in recent years. Here, we introduce the history of PROTAC, and summarize the recent advances in novel types of degradation technologies based on the PROTAC mechanism, including TF-PROTAC, Light-controllable PROTAC, PhosphoTAC, LYTAC, AUTAC, ATTEC, CMA, RNA-PROTAC and RIBOTACs. In addition, the clinical progress, current challenges and future prospects of degradation technologies based on PROTAC mechanism are discussed.

Keywords: E3 ligase; protein degradation technology; protein of interest; proteolysis-targeting chimeras.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cross-Linking Reagents* / chemistry
Proteolysis
RNA / metabolism
Ubiquitin-Protein Ligases* / metabolism

Substances

RNA
Ubiquitin-Protein Ligases
Cross-Linking Reagents

Grants and funding

This work was funded by the National Natural Science Foundation of China (grant nos. 81502065, 81672926 and 81972793) and the Natural Science Foundation of Shandong Province, China (ZR2021MC039).