REVIEW article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1676414
PROTAC: A Revolutionary Technology Propelling Small Molecule Drugs into the Next Golden Age
Provisionally accepted
- 1Yangzhou University Medical College, Yangzhou, China
- 2Yangzhou Jiangdu People's Hospital, Yangzhou, China
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Proteolysis Targeting Chimera (PROTAC) is a heterobifunctional molecule comprising three core components: a target protein ligand (typically a small-molecule inhibitor), a linker, and an E3 ubiquitin ligase ligand. By harnessing the specificity of the endogenous ubiquitin-proteasome system (UPS), PROTACs induce ubiquitination and subsequent degradation of target proteins. This technology constitutes an advanced therapeutic strategy for selective protein degradation, thereby expanding the horizons of drug design. Its significant therapeutic potential extends to treating cancers, viral infections (e.g., HIV and SARS-CoV-2), and chronic diseases. Recent clinical studies on compounds such as ARV-471 have yielded encouraging results, validating the efficacy of this approach. Over the past decade, PROTAC technology has garnered widespread attention in biomedicine for its promise in developing novel targeted therapies. This review will elucidate the broad therapeutic prospects and future challenges of PROTACs by detailing their mechanism of action, recent advances, progress in targeted therapy research, and current clinical trial landscape.
Keywords: PROTAC1, Protein degradation2, targeted therapy3, cancer4, Clinical progress5
Received: 30 Jul 2025; Accepted: 12 Sep 2025.
Copyright: © 2025 Cai, Chen, Wang, Zhang, Cui, Zhu and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qunshan Zhu, zhuqunshan@sohu.com
Haibo Sun, sun@yzu.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.