Bifunctional Molecules beyond PROTACs

J Med Chem. 2020 Mar 26;63(6):2802-2806. doi: 10.1021/acs.jmedchem.0c00293. Epub 2020 Mar 11.

Abstract

Heterobifunctional molecules, which recruit E3 ligases to ubiquitinate a target protein of interest, have found wide application as both biological tools and molecules with the potential to have clinical effects. In their recent paper, Yamazoe et al. report a heterobifunctional molecule that recruits the phosphatase PP1 to promote the dephosphorylation of pAKT to give AKT. This Viewpoint seeks to place this work in the wider context of heterobifunctional molecules and looks ahead to new possibilities presented by these results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Discovery
  • Humans
  • Ligands
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Interaction Maps / drug effects
  • Proteolysis / drug effects*
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination / drug effects

Substances

  • Ligands
  • Small Molecule Libraries
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex