Overview
- Wu, C. et al. (1997) J. Med. Chem. 40, 1690.
- Langleben, D. et al. (2004) Chest 126, 1377.
Alomone Labs Sitaxsentan inhibits ET-A receptor-mediated Ca2+ mobilization in CHO cells.Dose response plot of Sitaxsentan (#S-186) inhibition of the ET-A receptor-mediated, Endothelin-1-evoked Ca2+ mobilization. IC50 was determined at 11.67 nM. Cells were loaded with Calcium 6 dye, incubated with Sitaxsentan, and stimulated with 15 nM Endothelin-1 (EC80). Changes in intracellular Ca2+ levels were detected as changes in maximum relative fluorescence (RLU) using FLIPRTETRA™.
Sitaxsentan, is a synthetic compound that acts as a potent and selective antagonist of ET-A endothelin receptors. Sitaxsentan is one of the most selective ET-A antagonists reported1. Sitaxsentan inhibits Endothelin-1 radioligand binding to human ET-A and ET-B receptors with IC50 values of 1.4 nM and 9.8 µM, respectively1.
In pulmonary arterial hypertension clinical trials, sitaxsentan was shown to improve exercise capacity, improve functional capacity, and delay clinical worsening. However, the compound shows high liver toxicity and is no longer used to treat hypertension2.
Endothelin receptors include two subtypes: ET-A and ET-B. They are widely distributed in vascular and nonvascular tissues. ET-A receptors are predominantly detected in peripheral tissues, especially in vascular smooth muscle tissues to mediate vasoconstriction. They are also distributed in several regions of the brain.
ET-A has high affinity for endothelin-1 and endothelin-2 and relatively low affinity for endothelin-3, while the ET-B receptor has high affinity equally for all endothelin isopeptides3.
