VRT-043198，25MG，SML4133-25MG，Sigma

Biochem/physiol Actions

Orally available, highly potent and selective caspase-1 (ICE) inhibitor in vitro and in vivo.

VRT-043198, the active metabolite of VX-765 ( Belnacasan), is an orally available, highly potent and selective caspase-1 (ICE; Interleukin-1 converting enzyme) inhibitor (IC50/caspase- = 204 pM/1, 3.3 nM/8, 5.07 nM/9, 10.6 nM/5, 14.5 nM/4, 58.5 nM/14, 66.5 nM/10, >10 μM/3, 6 or 7). VRT-043198 inhibits IL-1β release from human PBMCs in cultures (IC50 = 0.67 μM) without affecting caspase-8/9-meidated apoptosis in Jurkat & NT2 cells. When administered orally in mice in vivo (25-100 mg/kg), VRT-043198 alleviates LPS-induced IL-1β production (50-100 mg/kg p.o. 1h prior to LPS i.v.) and is efficacious in a oxazolone-induced DTH dermatitis and a collagen-induced arthritis (CIA) model.