Belnacasan (VX-765)

Cas No.:	273404-37-8
Chemical Name:	VX 765; VX-765; VX765. Belnacasan
Synonyms:	VX 765; VX-765; VX765. Belnacasan
SMILES:	ClC1=C(N)C=CC(C(N[C@@H](C(C)(C)C)C(N2[C@H](C(N[C@H]3CC(O[C@H]3OCC)=O)=O)CCC2)=O)=O)=C1
Formula:	C24H33ClN4O6
M.Wt:	508.99

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