belnacasan

Belnacasan is an orally administered small molecule prodrug developed by Vertex Pharmaceuticals. It acts as a potent and selective inhibitor of caspase 1 (also known as interleukin-converting enzyme or ICE), and its active metabolite is VRT-043198[1][3][5]. Caspase 1 plays a central role in the activation of inflammatory cytokines such as IL-1β, IL-18, and IL-33, which are involved in inflammation and cell death pathways[3][5]. By inhibiting caspase 1, belnacasan reduces the release of these cytokines and moderates inflammatory responses. Preclinical studies have shown efficacy in models of epilepsy (including drug-resistant chronic epilepsy), rheumatoid arthritis, skin inflammation, multiple sclerosis, stroke, Alzheimer’s disease, atherosclerosis, and depressive-like behaviors[3][5]. In clinical trials it has been investigated for conditions including COVID-19 infection (Phase II), treatment-resistant epilepsy (Phase II; discontinued), psoriasis (discontinued), cardiovascular disorders (discontinued), cryopyrin-associated periodic syndromes (discontinued), and general inflammation-related diseases[4]. Despite being well tolerated in human trials so far, belnacasan has not demonstrated sufficient efficacy for approval in any indication to date but remains under investigation for new uses.

Other names

UNII-00OLE78529UNII00OLE78529UNII 00OLE78529