Keap1-Nrf2-IN-3

Keap1-Nrf2-IN-3 (also known as compound 37) is a potent, selective, non-covalent, and reversible small-molecule inhibitor of the protein-protein interaction (PPI) between Kelch-like ECH-associated protein 1 (KEAP1) and nuclear factor erythroid 2-related factor 2 (NRF2). It binds to the Kelch domain of KEAP1 with a dissociation constant (Kd) of 2.5 nM. By blocking the KEAP1-NRF2 interaction, Keap1-Nrf2-IN-3 prevents the ubiquitination and proteasomal degradation of NRF2, leading to its accumulation, nuclear translocation, and the subsequent activation of antioxidant response element (ARE)-driven cytoprotective genes. The compound was discovered through fragment-guided drug design in a collaborative effort between Astex Pharmaceuticals and GlaxoSmithKline (GSK). It is widely utilized as a high-quality chemical probe in research investigating oxidative stress, cellular defense mechanisms, neuroprotection, and oncology.

Other names

5-((1R,2R)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1-(3-(3-(2-propylpiperidine-1-carbonyl)phenyl)phenyl)-1H-pyrazole-4-carboxylic acid5RBKeap1-NRF2-IN3Keap-1-NRF2-IN3Keap 1-NRF2-IN3compound 37compound37compound-37