VRT-043198, the agent metabolite of VX-765 (Belnacasan), is a potent, selective and blood-brain barrier permeable inhibitor of interleukin-converting enzyme/caspase-1 subfamily caspases. It exhibits Ki values of 0.8 nM and 0.6 nM for ICE/caspase-1 and caspase-4, respectively.
- Exhibits 100- to 10,000-fold selectivity against other caspase-3 and -6 to -9.
- Inhibits the release of interleukin (IL)-1β and IL-18, but has little effect on the release of several other cytokines, including IL-1α, tumor necrosis factor-, IL-6 and IL-8.
- Inhibited IL-1β release from both PBMCs and whole blood with IC50 values of 0.67±0.55 and 1.9±0.80 nM, respectively.
- Lacks potent antiapoptotic activity.