Journal of Pharmaceutical Practice 2023;41(6):341-351

doi:10.12206/j.issn.2097-2024.202303008

Advances and prospects in targeted protein degradation

Luozhu ZHOU 1 ; Chunquan SHENG 1

Affiliations

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Keywords

targeted protein degradation; ubiquitin–proteasome system; lysosomal degradation pathway; drug discovery; PROTAC

Country

China

Language

Chinese

Abstract

Targeted protein degradation (TPD) techniques eliminate pathogenic proteins by hijacking the intracellular proteolysis machinery which includes the ubiquitin-proteasome system (UPS) and the lysosomal degradation pathway, holding promise to overcome the limitations of traditional inhibitors and further broaden the target space including many “undruggable” targets, and provide new targeted treatments for drug discovery. In this review, recent advances in a variety of promising TPD strategies were summarized, such as proteolysis targeting chimera (PROTAC), molecular glue, lysosome-targeting chimaera (LYTAC), autophagosome-tethering compound (ATTEC), autophagy-targeting chimera AUTAC and AUTOTAC, particularly. The representative case studies, potential applications and challenges were analyzed.