NT-0527

**NT-0527** is a highly potent, selective, brain-penetrant, and orally bioavailable small molecule inhibitor of the NLRP3 inflammasome, developed by NodThera Ltd. It potently suppresses NLRP3-mediated IL-1β production in human whole blood (IC50 0.79 μM) and peripheral blood mononuclear cells, with high selectivity over NLRC4 inflammasome and no effect on IL-6 or TNFα release. Demonstrating good pharmacokinetics, high passive permeability, and efficacy in a mouse peritonitis model (significant IL-1β inhibition at 10 mg/kg oral dose), it features favorable brain penetration properties (logD 2.32, Caco-2 Papp 34 × 10^-6 cm/s) suitable for neuroinflammatory disorders. Development was halted due to time-dependent inhibition of CYP2C19 (IC50 shift from 2.5 to 0.45 μM), positioning it as a valuable preclinical tool compound despite low aqueous solubility (7.3 μM).[1][2][3]