Proteolysis targeting chimeras (PROTACs) for epigenetics research

Curr Opin Chem Biol. 2020 Aug;57:8-16. doi: 10.1016/j.cbpa.2020.01.010. Epub 2020 Mar 5.

Abstract

Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules and allow selective protein degradation by addressing the natural ubiquitin proteasome system. As this new strategy of chemically induced protein degradation can serve as a biological tool and provides new possibilities for drug discovery, it has been applied to a variety of targets including (nuclear) receptors, kinases, and epigenetic proteins. A lot of PROTACs have already been designed in the field of epigenetics, and their synthesis and characterization highly contributed to structural optimization and improved mechanistic understanding of these molecules. In this review, we will discuss and summarize recent advances in PROTAC discovery with focus on epigenetic targets.

Keywords: Drug discovery; Epigenetics; PROTACs; Protein degradation.

Publication types

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

MeSH terms

  • Animals
  • Drug Discovery / methods*
  • Epigenesis, Genetic / drug effects*
  • Epigenomics / methods
  • Humans
  • Models, Molecular
  • Molecular Targeted Therapy / methods
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis / drug effects*
  • Ubiquitin / metabolism

Substances

  • Ubiquitin
  • Proteasome Endopeptidase Complex