Endothelin-Receptor Antagonists beyond Pulmonary Arterial Hypertension: Cancer and Fibrosis.
The endothelin axis and in particular the two endothelin receptors, ETA and ETB, are targets for therapeutic intervention in human diseases. Endothelin-receptor antagonists are in clinical use to treat pulmonary arterial hypertension and have been under clinical investigation for the treatment of several other diseases, such as systemic hypertension, cancer, vasospasm, and fibrogenic diseases. In this Perspective, we review the molecules that have been evaluated in human clinical trials for the treatment of pulmonary arterial hypertension, as well as other cardiovascular diseases, cancer, and fibrosis. We will also discuss the therapeutic consequences of receptor selectivity with regard to ETA-selective, ETB-selective, or dual ETA/ETB antagonists. We will also consider which chemical characteristics are relevant to clinical use and the properties of molecules necessary for efficacy in treating diseases against which known molecules displayed suboptimal efficacy.
Pneumology Division and Transplantation Center, Centre Hospitalier Universitaire Vaudois (CHUV) , CH1011 Lausanne, Switzerland.
John-David
JD
Aubert
University Institute of Pathology and Transplantation Center, Centre Hospitalier Universitaire Vaudois (CHUV), and University of Lausanne (UNIL), CH1011 Lausanne, Switzerland.
Lucienne
L
Juillerat-Jeanneret
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D065128:Endothelin Receptor Antagonists / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017466:Receptors, Endothelin / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D017466:Receptors, Endothelin