Tivantinib alleviates inflammatory diseases by directly targeting NLRP3.

ABSTRACT: NLRP3 inflammasome-mediated immune responses are involved in the pathogenesis of multiple inflammatory diseases, but few clinical drugs are identified that directly target the NLRP3 inflammasome to treat these diseases to date. Here, we show that the anticancer agent tivantinib is a selective inhibitor of NLRP3 and has a strong therapeutic effect on inflammasome-driven disease. Tivantinib specifically inhibits canonical and non-canonical NLRP3 inflammasome activation without affecting AIM2 and NLRC4 inflammasome activation. Mechanistically, Tivantinib inhibits NLRP3 inflammasome by directly blocking NLRP3 ATPase activity and subsequent inflammasome complex assembly. In vivo, Tivantinib reduces IL-1β production in mouse models of lipopolysaccharide (LPS)-induced systemic infla

SUBMITTER: Huang Y 

PROVIDER: S-EPMC9950949 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature