Belnacasan (VX765)

Description: Belnacasan (also known as VX-765) is a novel, potent, selective and orally bioactive prodrug of VRT-043198 which is a potent and selective inhibitor of caspase-1 with Ki values of 0.8 nM and less than 0.6 nM for caspase-1 and caspase-4, respectively. Belnacasan exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. Caspase-1 belongs to the IL-converting enzyme (ICE)/caspase-1 sub-family caspases. VX-765 is usually metabolized to an active molecular VRT-043198. In cultures of peripheral blood mononuclear cells stimulated with bacterial products, VRT-043198 inhibited the release of Interleukin (IL)-1β and IL-18, but had no affect the secretion of other cytokines such as IL-α, TNFα, IL-6 and IL-8. This product is also used in other models to illustrate the function of Caspase-1.