NP3-562 is a potent, orally bioavailable NLRP3 inflammasome inhibitor, inhibits IL-1β in nigericin-stimulated THP-1 cells with IC50 of 90 nM.
NP3-562 potently inhibits IL-1β in human whole blood after LPS/ATP stimulation with IC50 of 214 nM, and IC50 of 248 nM for mouse whole blood stimulated with LPS/ATP.
NP3-562 binds to the NLRP3 NACHT domain with IC50 of 0.26 uM in FP binding assays, shows a unique binding mode as compared to the known sulfonylurea-based inhibitors.
NP3-562 (50 mg/kg po) caused 90% IL-1β inhibition at 1.68 ± 0.53 μM blood concentration in female C57BL/6 mice.
NP3-562 shows a clean off-target profile, including no mutagenic findings, no interference with the NF-κB pathway (TNFα IC50>100 μM).
