Non-electrophilic modulators of the canonical Keap1/Nrf2 pathway

Bioorg Med Chem Lett. 2015 Jun 1;25(11):2261-8. doi: 10.1016/j.bmcl.2015.04.019. Epub 2015 Apr 16.

Abstract

Nrf2 is the major transcription factor that regulates many of the cytoprotective enzymes involved in the adaptive stress response. Modulation of Nrf2 could be therapeutically useful in a number of disease states. Activation can occur through either an electrophilic or non-electrophilic mechanism. To date, most of the research has focused on electrophilic Nrf2 activators, but there is increasing interest in non-electrophilic modulators of Nrf2. This Digest examines the current selection of small molecules that modulate Nrf2 through non-electrophilic mechanisms, and it highlights new opportunities for this important therapeutic target.

Keywords: Adaptive stress response; Cul3; Keap1; Nrf2; Nrf2 activator; Nrf2 repressor; Nrf2/Keap1 interaction; Protein–protein interaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kelch-Like ECH-Associated Protein 1
  • Models, Molecular
  • NF-E2-Related Factor 2 / agonists*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Protein Binding
  • Protein Conformation
  • Signal Transduction / drug effects*

Substances

  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2