In vivo synthetic chemistry of proteolysis targeting chimeras (PROTACs)

Bioorg Med Chem. 2021 Jul 1:41:116221. doi: 10.1016/j.bmc.2021.116221. Epub 2021 May 19.


Chemical knockdown of therapeutic targets using proteolysis targeting chimeras (PROTACs) is a rapidly developing field in drug discovery, but PROTACs are bifunctional molecules that generally show poor bioavailability due to their relatively high molecular weight. Recent developments aimed at the development of next-generation PROTACs include the in vivo synthesis of PROTAC molecules, and the exploitation of PROTACs as chemical tools for in vivo synthesis of ubiquitinated proteins. This short review covers recent advances in these areas and discusses the prospects for in vivo synthetic PROTAC technology.

Keywords: CLIPTACs; Chemical protein knockdown; In vivo synthetic chemistry; PROTACs; Ubiquitination.

Publication types

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

MeSH terms

  • Drug Discovery*
  • Humans
  • Molecular Targeted Therapy
  • Proteasome Endopeptidase Complex* / physiology
  • Proteolysis
  • Ubiquitin-Protein Ligases*


  • Proteasome Endopeptidase Complex
  • Ubiquitin-Protein Ligases