Advances in the preclinical and clinical research of proteolysis targeting chimera.
- Author:
Zhaoxiang LIU
1
;
Sen LIU
1
Author Information
- Publication Type:Journal Article
- Keywords: clinical research; drug resistance; proteolysis targeting chimera (PROTAC); target protein
- MeSH: Proteolysis; Proteolysis Targeting Chimera; Proteasome Endopeptidase Complex/metabolism*; Ubiquitin-Protein Ligases/metabolism*; Proteins/metabolism*; Ligands
- From: Chinese Journal of Biotechnology 2023;39(9):3615-3627
- CountryChina
- Language:Chinese
- Abstract: Proteolysis targeting chimera (PROTAC) refers to heterobifunctional small molecules that can simultaneously bind an E3 ubiquitin ligase and a target protein, enabling specific degradation of the target protein with the aid of the ubiquitin proteasome system. At present, most PROTAC drugs are in the clinical trial stage, and the ligands are mainly non-covalent compounds. PROTAC drugs have the advantage of overcoming drug resistance and degrading "undruggable" target proteins, but non-covalent ligands could lead to the hook effect that undermines drug efficacy. With its own advantages, covalent ligands can avoid the occurrence of this phenomenon, which is of great help to the development of PROTAC. This review summarizes the progress in preclinical and clinical research and application of PROTAC molecules targeting three different classes of protein targets, including intranuclear, transmembrane, and cytosolic proteins. We also offer perspective discussions to provide research ideas and references for the future development of PROTAC.
