2. Academic Validation
  3. Progress in the controllability technology of PROTAC

Progress in the controllability technology of PROTAC

  • Eur J Med Chem. 2024 Feb 5:265:116096. doi: 10.1016/j.ejmech.2023.116096.
Xin He 1,  Zhibing Weng 2,  Yi Zou 3
Affiliations

Affiliations

  • 1 School of Chemical and Pharmaceutical Engineering, Changzhou Vocational Institute of Engineering, Changzhou, 213164, PR China. Electronic address: [email protected].
  • 2 School of Chemical and Pharmaceutical Engineering, Changzhou Vocational Institute of Engineering, Changzhou, 213164, PR China.
  • 3 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address: [email protected].
PMID: 38160619 DOI: 10.1016/j.ejmech.2023.116096
Abstract

Proteolysis-targeting chimaera (PROTAC) technology functions by directly targeting proteins and catalysing their degradation through an event-driven mode of action, a novel mechanism with significant clinical application prospects for various diseases. Currently, the most advanced PROTAC drug is undergoing phase III clinical trials (NCT05654623). Although PROTACs exhibit significant advantages over traditional small-molecule inhibitors, their catalytic degradation of normal cellular proteins can potentially cause toxic side effects. Therefore, to achieve targeted release of PROTACs and minimize adverse reactions, researchers are actively exploring diverse controllable PROTACs. In this review, we comprehensively summarize the control strategies to provide a theoretical basis for the innovative application of PROTAC technology.

Keywords

CRBN; Controllability; PROTACs; Release the active molecule; VHL.

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