Darusentan

Darusentan (Lu-135252) is a selective endothelin receptor A (ET-A) receptor antagonist, which binds with a K_i of 1.4 nM to the ET-A receptor and a K_i of 184 nM to ET-B receptor, respectively with a 100-fold selectivity for ETA rather than ETB receptors^[1]. Darusentan competes for radiolabeled endothelin binding in rat aortic vascular smooth muscle cells (RAVSMs) membranes with single-site kinetics, exhibiting a K_i of 13 nM^[2]. In Vitro: Darusentan ((S)-Darusentan) competes for radiolabeled endothelin binding in rat aortic vascular smooth muscle cells (RAVSMs) membranes with single-site kinetics, exhibiting a K_i=13 nM. In isolated endothelium-denuded rat aortic rings, Darusentan inhibits endothelin-induced vascular contractility with a pA₂=8.1±0.14. Darusentan ( 0.001-1μM) inhibits ET-1-induced signaling in cultured RAVSMs^[2]. In Vivo: Darusentan (30 mg/kg per day orally for weeks 3 and 4) reverses aortic alterations produced by infusion of Norepinephrine (2.5 μg/kg per min subcutaneously for 2 and 4 weeks) in male Sprague Dawley rats^[3].