Sitaxentan (TBC11251, trade name Thelin) is a potent and selective Endothelin A receptor antagonist. Sitaxentan was under development by Encysive Pharmaceuticals (now Pfizer) for use in the treatment of pulmonary hypertension, congestive heart failure and asthma. It was launched in the major markets of the European Union (EU) under name Thelin for the treatment of pulmonary arterial hypertension. In December 2010, Pfizer discontinued clinical trials of sitaxentan worldwide and initiated voluntary product withdrawal from markets where it is approved due to life-threatening idiosyncratic risk of liver injury.

Tezosentan (Veletri; Ro 61–0612) is a dual endothelin receptor antagonist that has been shown to improve cardiac output, decrease pulmonary capillary wedge pressure, and reduce pulmonary and systemic vascular resistance in initial clinical studies in acutely decompensated heart failure. Tezosentan is a water-soluble ET-1 receptor antagonist with high affinity to both ETA and ETB receptors but greater potency for the ETA receptor subtype. Clinical studies demonstrated mixed results for Tezosentan regarding its efficacy and tolerability in the management of decompensated heart failure. The side effects of Tezosentan include a headache, nausea, and hypotension.

Ambrisentan (alternative Names: BSF 208075; GSK 1325760; GSK1325760A; Letairis) is an endothelin receptor antagonist that is selective for the endothelin type-A (ETA) receptor. The chemical name of ambrisentan is (+)-(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid. Ambrisentan is indicated for the treatment of pulmonary arterial hypertension. It is approved in Europe, Canada and the United States for use as a single agent to improve exercise ability and delay clinical worsening. In addition, it is approved in the United States for use in combination with tadalafil to reduce the risks of disease progression, hospitalization and to improve exercise ability. As an endothelin receptor antagonist, ambrisentan prevents endogenous endothelin peptide from constricting the muscles in blood vessels, allowing them to relax and permit a reduction in blood pressure. Endothelin-1 (ET-1) is a potent autocrine and paracrine peptide. Two receptor subtypes, ETA and ETB, mediate the effects of ET-1 in the vascular smooth muscle and endothelium. The primary actions of ETA are vasoconstriction and cell proliferation, while the predominant actions of ETB are vasodilation, antiproliferation, and ET-1 clearance. In patients with PAH, plasma ET-1 concentrations are increased as much as 10-fold and correlate with increased mean right atrial pressure and disease severity. ET-1 and ET-1 mRNA concentrations are increased as much as 9-fold in the lung tissue of patients with PAH, primarily in the endothelium of pulmonary arteries. These findings suggest that ET-1 may play a critical role in the pathogenesis and progression of PAH. Ambrisentan is a high-affinity (Ki=0.011 nM) ETA receptor antagonist with a high selectivity for the ETA versus ETB receptor (>4000-fold). The clinical impact of high selectivity for ETA is not known.

Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer®. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure. Bosentan competitively antagonizes the binding of 125I-labeled ET-1 to human vascular smooth muscle cells (predominantly ETA receptors) with an inhibition constant (Ki ) of 4.7 nM and to human placenta membranes (predominantly ETB receptors) with a Ki of 95 nM. Furthermore, bosentan is specific for endothelin receptors and does not interfere with the binding of a variety of peptides, neurotransmitters, growth factors, or eicosanoids to their receptors.

Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer®. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure. Bosentan competitively antagonizes the binding of 125I-labeled ET-1 to human vascular smooth muscle cells (predominantly ETA receptors) with an inhibition constant (Ki ) of 4.7 nM and to human placenta membranes (predominantly ETB receptors) with a Ki of 95 nM. Furthermore, bosentan is specific for endothelin receptors and does not interfere with the binding of a variety of peptides, neurotransmitters, growth factors, or eicosanoids to their receptors.

Atrasentan (ABT-627, A-127722) is a selective endothelin A receptor antagonist. Atrasentan is being developed by AbbVie as an oral treatment for diabetic nephropathies.Abbott Laboratories was conducting clinical development of atrasentan for the treatment of certain cancers, including phase II trials for prostate cancer. However, no recent development has been reported for cancer indications and development is presumed to be discontinued.

Atrasentan (ABT-627, A-127722) is a selective endothelin A receptor antagonist. Atrasentan is being developed by AbbVie as an oral treatment for diabetic nephropathies.Abbott Laboratories was conducting clinical development of atrasentan for the treatment of certain cancers, including phase II trials for prostate cancer. However, no recent development has been reported for cancer indications and development is presumed to be discontinued.

Enrasentan is an orally active mixed endothelin A/B receptor antagonist with a 100-fold greater affinity for the endothelin A receptor. In an animal model of hypertension and cardiac hypertrophy the drug has reduced blood pressure, prevented cardiac hypertrophy and preserved myocardial function. In rats with hyperinsulinemia and hypertension enrasentan normalized blood pressure and prevented cardiac and renal damage. In rats with stroke the drug reduced the ischemic area in the brain. Enrasentan had been in phase II clinical trial for the treatment of heart failure but the results suggested that enrasentan does not appear to have favorable effects on ventricular remodeling.

Atrasentan (ABT-627, A-127722) is a selective endothelin A receptor antagonist. Atrasentan is being developed by AbbVie as an oral treatment for diabetic nephropathies.Abbott Laboratories was conducting clinical development of atrasentan for the treatment of certain cancers, including phase II trials for prostate cancer. However, no recent development has been reported for cancer indications and development is presumed to be discontinued.