GSK461364 Inhibits NLRP3 Inflammasome by Targeting NEK7 Phosphorylation.

ABSTRACT: NLRP3 inflammasome is a multiple protein complex sensing exogenous or endogenous stimuli, and aberrant activation of the NLRP3 inflammasome is implicated in various inflammatory disorders. While numerous small-molecule compounds targeting NLRP3 inflammasome activity have been developed, most have encountered limited success in clinical translation. Through screening of a kinase compound library, GSK461364 is identified as a potent and selective NLRP3 inflammasome inhibitor. Notably, GSK461364 confers significant protective effects in murine models of LPS-induced endotoxemia and DSS-induced colitis. Mechanistic study reveals that GSK461364 exerts its inhibitory effects via targeting Polo-like Kinase 1(PLK1). Specifically, that PLK1-mediated phosphorylation of NEK7, likely occurring at evolu

SUBMITTER: Luo R 

PROVIDER: S-EPMC12667451 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature