tcsc2766 Belnacasan (VX-765)

Belnacasan (VX-765) is an oral prodrug of VRT-043198, a potent and selective caspase-1 inhibitor with a K_i of 0.8 nM.

IC50 & Target: Caspase-1^[1]

In Vitro: Belnacasan inhibits the release of LPS-induced IL-1β and IL-18 by human PBMCs with an IC₅₀ of ~0.7 μM and reduces inflammatory response in murine models of inflammatory disease^[1]. VBelnacasan is a potent, specific inhibitor of the caspase-1 subfamily^[2].

In Vivo: Belnacasan doses 50, 100, and 200 mg/kg significantly (p<0.05) reduces serum IL-1β levels by as much as 60%, whereas 25 mg/kg has a smaller effect (~35% inhibition) that is not statistically significant. It is noteworthy that the effect of Belnacasan on the release of IL-1β induced by LPS reached a plateau at 100 mg/kg. Belnacasan (25, 50, and 100 mg/kg × 2) significantly reduces ear edema. Belnacasan also dose-dependently reduces the concentrations of cytokines, chemokines, and inflammatory mediators in the ear biopsy samples^[2]. Belnacasan at doses of 25, 50, and 200 mg/kg significantly delays the time to seizure onset by 1.5- to twofold (p<0.01), reduces the number of seizures by 40% (p<0.01) and the total time spent in EEG seizure activity by 30 to 50% (p<0.01)^[3].