Overview
- Riechers, H. et al. (1996) J. Med. Chem. 39, 2123.
- Liang, F. et al. (2010) Can. J. Physiol. Pharmacol. 88, 840.
- Prié, S. et al. (1997) J. Pharmacol. Exp. Ther. 282, 1312.
Alomone Labs Darusentan inhibits ET-A receptor-mediated Ca2+ mobilization in CHO-K1 cells.Dose response curve of Darusentan (#D-265) inhibition of ET-A receptor-mediated, Endothelin-1-evoked Ca2+ mobilization. IC50 was determined at 10.96 nM.
Cells were loaded with Calcium 6 dye, incubated with Darusentan, and stimulated with 15 nM Endothelin-1 (EC80). Changes in intracellular Ca2+ levels were detected as changes in maximum relative fluorescence (RLU) using FLIPRTETRA™.
Darusentan, (LU 135252), is a synthetic compound that acts as a selective antagonist of endothelin A (ET-A) receptors. Darusentan is orally bioavailable and is a potent inhibitor of vasoconstriction in large and small arteries. The compound is a propanoic acid based antagonist that consist of two enantiomers - (R) and (S). The (R) enantiomer shows no binding activity, indicating that the (S) enantiomer is the active drug1,2.
in vitro, Darusentan inhibits endothelin-induced vascular contractility in isolated endothelium-denuded rat aortic rings with pA2 value of 8.11,2.
Endothelin receptors include two subtypes: ET-A and ET-B. They are widely distributed in vascular and nonvascular tissues. ET-A receptors are predominantly expressed in peripheral tissues, especially in vascular smooth muscle tissues to mediate vasoconstriction. They are also detected in several different regions of the brain3.
