https://www.selleckchem.com/products/Methazolastone.html 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.The 2019-20 wildfires in eastern Australia presented a globally important opportunity to evaluate the respective roles of climatic drivers and natural and anthropogenic disturbances in causing high-severity fires. Here, we show the overwhelming dominance of fire weather in causing complete scorch or consumption of forest canopies in natural and plantation forests in three regions across the geographic range of these fires. Sampling 32% (2.35 Mha) of the area burnt we found that >44% of the native forests suffered severe canopy damage. Past logging and wildfire disturbance in natural forests had a very low effect on severe canopy damage, reflecting the limited