darusentan

Description: Darusentan (formerly LU-135252 or HMR-4005) is an endothelin receptor antagonist (ERA)/inhibitor. It is a propanoic acid based ERA currently in phase 3 clinical trials for resistant hypertension. In vascular smooth muscle, (S)-darusentan is an ERA with high affinity for the ET receptor, which in this preparation is predominantly ETA receptors. (S)-Darusentan inhibits endothelin-induced signaling related to pro-contractile activity and is a potent inhibitor of vasoconstriction in large and small arteries. Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats. Endothelin is a potent vasoconstrictor often up-regulated in hypertension. Endothelin vasoconstriction is mediated via the G-protein coupled endothelin A (ETA) receptor present on vascular smooth muscle. Endothelin receptor antagonists (ERAs) have been shown to antagonize ET-induced vasoconstriction.

References: Can J Physiol Pharmacol. 2010 Aug; 88(8):840-9; Hepatology. 2014 Mar; 59(3):1107-17.