ARTICLE
Volume 10,Issue 4
9 February 2026
Advances in Proteolysis Targeting Chimeras
Shili Liu ,
Yu Liu
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1
China Pharmaceutical University, Nanjing 210000, Jiangsu, China,
PAR 2026 , 10(1), 69–83;
https://doi.org/10.26689/par.v10i1.13504
© 2026 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract
In recent years, proteolysis-targeting chimeras (PROTACs) have gained widespread attention as an emerging therapeutic approach. PROTACs are bifunctional molecules composed of a target protein-binding ligand, an E3 ubiquitin ligase ligand, and a linker connecting these ligands. By harnessing the cell’s intrinsic ubiquitin-proteasome system (UPS), they promote the ubiquitination of specific target proteins, leading to their degradation and therapeutic effects. PROTACs show exceptional promise in targeting conventional “undruggable” targets compared to traditional small-molecule inhibitors. This review provides an overview of PROTACs, including their molecular mechanism of action, therapeutic benefits, development history, key design aspects, current research and development challenges, and future trends in next-generation PROTAC technology.
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