Targeted protein degradation as a powerful research tool in basic biology and drug target discovery

Nat Struct Mol Biol. 2020 Jul;27(7):605-614. doi: 10.1038/s41594-020-0438-0. Epub 2020 Jun 15.

Abstract

Controlled perturbation of protein activity is essential to study protein function in cells and living organisms. Small molecules that hijack the cellular protein ubiquitination machinery to selectively degrade proteins of interest, so-called degraders, have recently emerged as alternatives to selective chemical inhibitors, both as therapeutic modalities and as powerful research tools. These systems offer unprecedented temporal and spatial control over protein function. Here, we review recent developments in this field, with a particular focus on the use of degraders as research tools to interrogate complex biological problems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Drug Discovery / methods*
  • Humans
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Indoleacetic Acids / metabolism
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Proteins / metabolism*
  • Proteolysis / drug effects
  • Small Molecule Libraries / pharmacology
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Ubiquitination / drug effects

Substances

  • Immunologic Factors
  • Indoleacetic Acids
  • Proteins
  • Small Molecule Libraries
  • Sulfonamides