CIB-1476 is an irreversible covalent inhibitor of pro-caspase-1 with IC50 of 0.65 uM, covalently targets pro-caspase-1 Cys285 and Cys397, inhibits NLRP3 inflammasome activation.
CIB-1476 has no effect on pro-caspase-1 and pro-IL-1β protein expression, but potently inhibited the expression of the p20 fragment of caspase-1 and mature IL-1β stimulated by various NLRP3 agonists.
CIB-1476 significantly inhibited the release of IL-1β and IL-18 in LPS and nigericin-stimulated J774A.1 cells in a concentration-dependent manner. Meanwhile, CIB-1476 also effectively inhibited ATP- and MSU-induced NLRP3 inflammasome activation.
CIB-1476 blocks the noncanonical function of caspase-1 in the suppression of priming and assembly of the NLRP3 inflammasome.
CIB-1476 effectively suppressed pyroptosis during NLRP3 inflammasome activation.
CIB-1476 effectively inhibited NLRP3 inflammasome activation in vivo against caspase-1-mediated inflammation in mice.