NIC-11 is a highly potent broad-spectrum NLRP3 inhibitor, inhibits NLRP3 inflammasome activation (IL-1β release) in mouse macrophages with IC50 of 69 nM.
NIC-11 dose-dependently inhibited LDH release in mouse BMDMs.
NIC-11 targets NLRP3 signaling upstream of caspase-1 in mouse BMDMs, does not target NLRP3 priming.
NIC-11 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-11 shows potent activity in LPS-stimulated blood monocytes and dose-dependently inhibited IL-1ß secretion with IC50 of 16 nM in primary human monocytes.
NIC-11 shows direct binding to the NLRP3 NACHT domain with IC50 of 212 nM in NanoBRET target engagement assays.
NIC-11 inhibits pyroptosis of MWS-associated Nlrp3A350V BMDMs.
NIC-11(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.