YQ128 is a potent and selective second-generation NLRP3 (NOD-like receptor P3) inflammasome inhibitor with an IC50 of 0.30 μM. YQ128 significantly and selectively suppresses the production of IL-1β, but not TNF-α, and it can cross the BBB to reach the CNS. YQ128 has anti-inflammatory activity.In Vitro: YQ128 (0.3-100 μM; 30 mins) dose dependently suppressed the release of IL-1β from peritoneal macrophages upon LPS/ATP challenge with an IC50 of 1.59 μM.
YQ128 (20 μM; 2 hours) shows no significant toxic effects on hCMEC/D3 cells.
In Vivo: YQ128 (iv; 20 mg/kg) has an intermediate terminal plasma half-life (t1/2) of 6.6 hours after iv administration.
YQ128 (oral; 20 mg/kg) shows delayed gastrointestinal absorption with a tmax and cmax of 12 h and 73 ng/mL, respectively. Oral bioavailability (Foral) is estimated as 10%.
YQ128 exhibits extensive extravascular distribution with a large steady-state volume of distribution (Vdss) of 8.5 L/kg and rapid total clearance (CLtot) of 41 mL/min/kg.
YQ128 (10 mg/kg) has been shown to trigger IL-1β production in a NLRP3- dependent manner in C57BL/6 mice.