Recent progress in Keap1-Nrf2 protein-protein interaction inhibitors

Eur J Med Chem. 2020 Sep 15:202:112532. doi: 10.1016/j.ejmech.2020.112532. Epub 2020 Jul 6.

Abstract

Therapeutic targeting the protein-protein interaction (PPI) of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its main regulator, Kelch-like ECH-Associating protein 1 (Keap1) has been emerged as a feasible way to combat oxidative stress related diseases, due to the key role of Nrf2 in oxidative stress regulation. In recent years, many efforts have been made to develop potent Keap1-Nrf2 inhibitors with new chemical structures. Various molecules with diverse chemical structures have been reported and some compounds exhibit high potency. This review summarizes peptide and small molecule Keap1-Nrf2 inhibitors reported recently. We also highlight the pharmacological effects and discuss the possible therapeutic application of Keap1-Nrf2 inhibitors.

Keywords: Keap1; Nrf2; Protein-protein interaction inhibitors.

Publication types

  • Review

MeSH terms

  • Humans
  • Kelch-Like ECH-Associated Protein 1 / antagonists & inhibitors*
  • Kelch-Like ECH-Associated Protein 1 / chemistry
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Molecular Structure
  • NF-E2-Related Factor 2 / antagonists & inhibitors*
  • NF-E2-Related Factor 2 / chemistry
  • NF-E2-Related Factor 2 / metabolism
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Protein Binding / drug effects
  • Signal Transduction / drug effects
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*

Substances

  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Peptides
  • Small Molecule Libraries