Monomeric Targeted Protein Degraders

J Med Chem. 2020 Oct 22;63(20):11330-11361. doi: 10.1021/acs.jmedchem.0c00093. Epub 2020 Jun 15.


The discovery and development of targeted protein degraders have become important areas of research in the field of medicinal chemistry. Inducing degradation of a target protein presents several advantages relative to simple inhibition including a potential for extended duration of action and more profound pharmacology. While engineered heterodimeric molecules have recently been a major focus within industry and academia, this Perspective highlights examples of targeted protein degradation observed for smaller, monomeric molecules. Methods and tools for evaluating protein degradation as well as a discussion of physical properties of monomeric vs engineered heterodimeric degraders are presented.

Publication types

  • Review

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Drug Discovery / methods*
  • Humans
  • Molecular Structure
  • Protein Binding
  • Proteins / antagonists & inhibitors
  • Proteolysis / drug effects*
  • Small Molecule Libraries* / chemistry
  • Small Molecule Libraries* / pharmacology
  • Ubiquitin-Protein Ligases


  • Proteins
  • Small Molecule Libraries
  • Ubiquitin-Protein Ligases