Advances and perspectives of proteolysis targeting chimeras (PROTACs) in drug discovery

Bioorg Chem. 2022 Aug;125:105848. doi: 10.1016/j.bioorg.2022.105848. Epub 2022 May 5.


Proteolysis-targeting chimeras (PROTACs), bifunctional molecules consisting of a ligand of protein of interest (POI), an E3 ligase ligand and a linker, have been developed to hijack the ubiquitin-proteasome system (UPS) to induce different POIs degradation. Currently, the first oral PROTACs (ARV-110 and ARV-471) have shown encouraging efficacy in clinical trials of prostate and breast cancer treatment, which turns a new avenue for the development of PROTAC research. In this review, we focus on a detailed summary of the latest progress of PROTACs and elucidate the advantages of PROTACs technology. In addition, potential challenges and perspectives of PRTOACs are discussed.

Keywords: Drug discovery; PROTACs; Small inhibitors; Target protein degradation; Undruggable target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Drug Discovery*
  • Ligands
  • Proteolysis*
  • Ubiquitin-Protein Ligases*


  • Ligands
  • Ubiquitin-Protein Ligases