Bosentan is a competitive and dual antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors.
IC50 value:
Target: ETA/ETB receptor
Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes constriction of the pulmonary blood vessels. By blocking this interaction, bosentan decreases pulmonary vascular resistance. Bosentan has a slightly higher affinity for ET-A than ET-B. Bosentan is indicated mainly for the treatment of pulmonary hypertension. In 2007, Bosentan was also approved in the European Union for reducing the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease.

ACT-132577

ACT-132577 is the major and pharmacologically active metabolite of macitentan(ACT-064992), which is dual ETA/ETB endothelin (ET) receptor antagonist designed for tissue targeting.
IC50 value:
Tareget: ETA/ETA receptor
In vivo, macitentan is metabolized into a major and pharmacologically active metabolite, ACT-132577. Macitentan and its metabolite antagonized the specific binding of ET-1 on membranes of cells overexpressing ET(A) and ET(B) receptors and blunted ET-1-induced calcium mobilization in various natural cell lines, with inhibitory constants within the nanomolar range. In functional assays, macitentan and ACT-132577 inhibited ET-1-induced contractions in isolated endothelium-denuded rat aorta (ET(A) receptors) and sarafotoxin S6c-induced contractions in isolated rat trachea (ET(B) receptors). In rats with pulmonary hypertension, macitentan prevented both the increase of pulmonary pressure and the right ventricle hypertrophy, and it markedly improved survival [1]. In both ethnic groups, females had an approximately 15% higher exposure to ACT-132577 than male subjects [2]. ACT-132577, a metabolite with lower potency than macitentan, had a half-life of about 48?hours and accumulated approximately 8.5-fold [3].