VX-765 is anally absorbed prodrug of VRT-043198, which exhibits potent inhibition against ICE/caspase-1 caspase-4 with Ki of 0.8 nM less than 0.6 nM, respectively. VRT-043198 also inhibits IL-1β release from both PBMCs whole blood with IC50 of 0.67 μM 1.9 μM, respectively.
体内研究
In collagen-induced arthritis mouse model, VX-765 (200 mg/kg) inhibits LPS-induced IL-1β production by about 60%, results in a dose-dependent, statistically significant reduction in the inflammation scores effective protection fromt changes. In vivo, VX-765 blocks kindling epileptogenesis in rats by preventing IL-1β increase in forebrain astrocytes without significant effect on afterdischarge duration. In the mouse model of acute seizures, VX-765 (50 mg/kg-200 mg/kg) produces the anticonvulsant effect by delaying the time to onset of the first seizure decreasing the number of seizures as well as their total duration by average 50% 64%. In adult rats with genetic absence epilepsy (GAERS), VX-765, after the 3rd drug injection, significantly reduces the cumulative duration number of spike-and-wave discharges (SWDs) by 55% on average byively blocking IL-1β biosynthesis.
特征
VX-765 is a potentive inhibitof interleukin-converting enzyme/caspase-1.
