CH7450924, a KEAP1-NRF2 interaction inhibitor, ameliorates LPS-induced multiple organ dysfunction via inflammatory pathway inhibition.

ABSTRACT: Multiple organ dysfunction syndrome (MODS) claims a life every few seconds worldwide and is a severe condition that can affect people of all ages. Despite the availability of various treatments, the unmet medical needs remain high. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key molecule involved in biological protection and is expected to be beneficial for MODS, but its role in ameliorating MODS remains unknown. We identified a novel kelch-like ECH-associated protein 1 (KEAP1)-NRF2 protein-protein interaction inhibitor, CH7450924, and evaluated its efficacy in lipopolysaccharide (LPS)-induced MODS models. To characterize our compound, we analyzed CH7450924 binding to KEAP1 by crystallography. Comprehensive binding and inhibition experiments were conducted to evaluate selectivi

SUBMITTER: Hoshino M 

PROVIDER: S-EPMC12534457 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature