rrx-001 has been researched along with Colitis* in 1 studies
1 other study(ies) available for rrx-001 and Colitis
Article | Year |
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RRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor.
The NLRP3 inflammasome plays a crucial role in innate immune-mediated inflammation and contributes to the pathogenesis of multiple autoinflammatory, metabolic and neurodegenerative diseases, but medications targeting the NLRP3 inflammasome are not available for clinical use. RRx-001 is a well-tolerated anticancer agent currently being investigated in phase III clinical trials, but its effects on inflammatory diseases are not known. Here, we show that RRx-001 is a highly selective and potent NLRP3 inhibitor that has strong beneficial effects on NLRP3-driven inflammatory diseases. RRx-001 inhibits the activation of the canonical, noncanonical, and alternative NLRP3 inflammasomes but not the AIM2, NLRC4 or Pyrin inflammasomes. Mechanistically, RRx-001 covalently binds to cysteine 409 of NLRP3 via its bromoacetyl group and therefore blocks the NLRP3-NEK7 interaction, which is critical for the assembly and activation of the NLRP3 inflammasome. More importantly, RRx-001 treatment attenuates the symptoms of lipopolysaccharide (LPS)-induced systemic inflammation, dextran sulfate sodium (DSS)-induced colitis and experimental autoimmune encephalomyelitis (EAE) in mice. Thus, our study identifies RRx-001 as a new potential therapeutic agent for NLRP3-driven diseases. Topics: Animals; Azetidines; CARD Signaling Adaptor Proteins; Colitis; Cysteine; Dextran Sulfate; Encephalomyelitis, Autoimmune, Experimental; Inflammasomes; Inflammation; Lipopolysaccharides; Macrophages; Mice, Inbred C57BL; NIMA-Related Kinases; Nitro Compounds; NLR Family, Pyrin Domain-Containing 3 Protein; Protein Domains | 2021 |