Keap1-Nrf2 PPI inhibitor

Keap1-Nrf2 PPI inhibitors are a class of small-molecule therapeutics designed to disrupt the protein-protein interaction (PPI) between Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2). Under physiological conditions, Keap1 acts as a substrate adaptor for the Cullin 3 (Cul3)-based E3 ubiquitin ligase complex, targeting Nrf2 for ubiquitination and subsequent proteasomal degradation. By blocking the Keap1-Nrf2 interaction, these inhibitors prevent Nrf2 degradation, allowing it to accumulate and translocate to the nucleus. Once in the nucleus, Nrf2 binds to the antioxidant response element (ARE) to drive the transcription of cytoprotective and antioxidant genes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). This pathway activation enhances cellular defense against oxidative stress and inflammation, offering therapeutic potential in conditions like acute kidney injury, chronic kidney disease, and other inflammatory or degenerative disorders.

Other names

Keap1-Nrf2 inhibitorKeap-1-Nrf2 inhibitorKeap 1-Nrf2 inhibitorKeap1-Nrf2 interaction inhibitorKeap-1-Nrf2 interaction inhibitorKeap 1-Nrf2 interaction inhibitorKeap1-Nrf2 protein-protein interaction inhibitorKeap-1-Nrf2 protein-protein interaction inhibitorKeap 1-Nrf2 protein-protein interaction inhibitorKeap1/Nrf2 PPI inhibitor