NLRP3-IN-20 (compound 11) is an orally administered inhibitor targeting the NLRP3 inflammasome, exhibiting potent inhibition with an IC50 of 25 nM against IL-1β secretion. It possesses excellent pharmacokinetic properties and has shown significant efficacy in models of non-alcoholic steatohepatitis, fatal septic shock, and colitis [1].

Pharmacokinetic analysis in mice [1] showed that an intravenous (i.v.) administration of the compound at a dose of 5 mg/kg resulted in a half-life (T 1/2) of 4.01 hours, time to peak concentration (T max) of 0.083 hours, peak concentration (C max) of 22567 ng/mL, area under the curve from time zero to infinity (AUC 0-inf) of 130240 ng·h/mL, mean residence time from time zero to infinity (MRT 0-inf) of 5.30 hours, volume of distribution (V z) of 226 mL/kg, clearance (Cl) of 38.8 mL/h/kg, and absolute bioavailability (F) of -%. In contrast, oral administration (p.o.) of a 10 mg/kg dose showed a T 1/2 of 3.50 hours, T max of 0.667 hours, C max of 33867 ng/mL, AUC 0-inf of 221955 ng·h/mL, MRT 0-inf of 4.79 hours, and an F of 85.21%.