VX-765

VX-765 is a novel and irreversible IL-converting enzyme/caspase-1 inhibitor with an IC50 of 0.8 nM. VRT-043198, a potent and selective inhibitor of ICE/caspase-1 sub-family caspases is an active metabolite VX-765. VRT-043198 exhibits 100-10,000-fold selectivity against other caspase-3 and -6-9. VX-765 was efficiently converted to VRT-043198 when administered orally to mice and inhibited LPS-induced cytokine secretion. VX-765 has been shown to inhibit acute partial seizures in preclinical models and has shown activity in preclinical models of chronic partial epilepsy that do not respond to currently available medicines for epilepsy. In addition, VX-765 reduced disease severity and the expression of inflammatory mediators in models of rheumatoid arthritis and skin inflammation.