ML345 is a potent and selective NLRP3 inflammasome inhibitor with anti-inflammatory activity.

ABSTRACT: Excessive activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome plays a key role in the pathogenesis of various inflammatory diseases. Despite the development of several NLRP3 inhibitors, no specific therapy has been approved for clinical use, underscoring the urgent need for safe and effective agents. Here, we demonstrate that ML345 acts as a highly potent and selective NLRP3 inhibitor with strong therapeutic potential for NLRP3-driven inflammation. ML345 effectively suppresses canonical, noncanonical, and alternative NLRP3 inflammasome activation pathways, without affecting other inflammasomes. Mechanistically, ML345 blocks NLRP3 inflammasome activation independently of its intrinsic insulin-degrading enzyme (IDE) inhibitory activity. ML345 binds to N

SUBMITTER: Lin H 

PROVIDER: S-EPMC12615901 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature