NIC-12 is a highly potent broad-spectrum NLRP3 inhibitor, inhibits NLRP3 inflammasome activation (IL-1β release) in mouse macrophages with IC50 of 11 nM.
NIC-12 dose-dependently inhibited LDH release in mouse BMDMs.
NIC-12 targets NLRP3 signaling upstream of caspase-1 in mouse BMDMs, does not target NLRP3 priming.
NIC-12 suppresses LPS-induced NLRP3 activation downstream of TLR4-induced NF-κB signaling, also blocks the activation of the NLRP3 inflammasome by the endogenous STING agonist cGAMP in primary human monocytes.
NIC-12 shows potent activity in LPS-stimulated blood monocytes and dose-dependently inhibited IL-1ß secretion with IC50 of 8 nM in primary human monocytes.
NIC-12shows direct binding to the NLRP3 NACHT domain with IC50 of 131 nM in NanoBRET target engagement assays.
NIC-12 inhibits pyroptosis of MWS-associated Nlrp3A350V BMDMs.
NIC-12 (50 mg/kg) selectively reduces circulating IL-1ß levels in the LPS-endotoxemia model in mice and inhibits NLRP3 inflammasome activation in CAPS patient monocytes and mouse macrophages.