Ambrisentan(BSF 208075; LU 208075) is an oral, once-daily endothelin receptor antagonist that is selective for the endothelin type A receptor.
IC50 value:
Target: ETA receptor
Ambrisentan is indicated for the treatment of pulmonary arterial hypertension (PAH). Once daily oral ambrisentan 2.5 to 10 mg/day significantly improved exercise capacity (6-minute walk distance) compared with placebo in two double-blind, multicenter trials (ARIES-1 & ARIES-2). A decrease in dyspnea and a delay in clinical worsening were among the improvements in secondary outcomes generally observed with ambrisentan versus placebo. In ARIES-E, a 2-year extension of ARIES-1 and -2, approved dosages of ambrisentan (5 and 10mg/day) were associated with a sustained improvement in 6MWD, a generally sustained improvement in dyspnea, and a low risk of clinical worsening and of death. Six months' treatment with ambrisentan 5mg/day significantly improved 6MWD (primary outcome measure) and dyspnea relative to baseline in an open-label, non-comparative, multicenter study in a diverse population of patients with PAH or non-PAH forms of pulmonary hypertension. 

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].