VX-765 is an orally-available prodrug of VRT-043198, an inhibitor of interleukin-converting enzyme / caspase-1 subfamily caspases. VRT-043198 shows Ki values of 0.8 nM and 100-fold selectivity over other non-ICE subfamily caspases. VRT-043198 showed no significant activity towards trypsin or cathepsin B. (1)

VRT-043198 inhibits IL-1b release from both PBMCs and whole blood with IC50 values of 0.67 and 1.9 uM, respectively. Additionally in stimulated PBMCs, VRT-043198 dose-dependently inhibited IL-1b, IL-18, and IFN-g, without affecting TNF-a release. In a hypoxia-induced apoptosis assay employing the NT2 human neuroblastoma cell line, VRT-043198 did not alter ischemia-induced apoptosis up to concentrations of 100 uM. (1)

According to Vertex's news release , VX-765 has been shown to inhibit acute seizures in preclinical models of acute epilepsy and has shown activity in preclinical models of chronic epilepsy that do not respond to standard anti-epileptic drugs. (2)