NLRP3-IN-75 is an orally effective inhibitor of NLRP3, capable of suppressing IL-1β secretion with an IC50 of 23 nM. It selectively inhibits NLRP3 activation by disrupting inflammasome assembly without affecting the assembly of NLRC4 or AIM2 inflammasomes. NLRP3-IN-75 demonstrates excellent anti-inflammatory effects in models of acute peritonitis, diabetic nephropathy, and inflammatory bowel disease (IBD).