Identification and study of new NF-κB-inducing kinase ligands derived from the imidazolone scaffold.

ABSTRACT: Chronic kidney disease (CKD) is a growing health concern, projected to be a major cause of death by 2040, due to an increasing risk of acute kidney injury (AKI). Systems biology-derived data suggest that the unmet need for an orally available drug to treat AKI and improve CKD outcomes may be addressed by targeting kidney inflammation and, specifically, nuclear factor κB-inducing kinase (NIK), a key signaling molecule that activates the noncanonical nuclear factor κB (NF-κB) pathway. We have prepared and identified a small family of imidazolone derivatives that bind NIK and inhibit the noncanonical NF-κB activation pathway. The introduction of heterocyclic substituents in position 2 of the imidazolone core provides compounds with affinity against human NIK. Three candidates, with best affin

SUBMITTER: Maqueda-Zelaya F 

PROVIDER: S-EPMC11704032 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature