Endothelin-receptor antagonists: current and future perspectives

Despite much effort over recent years to design and develop endothelin-receptor antagonists, these compounds are far from becoming new drug entities. This article will review preclinical data on select endothelin-receptor antagonists as well as clinical data on bosentan, the only molecule currently in Phase III clinical trials. Though efficacious, bosentan is less potent than the angiotensin converting enzyme (ACE) inhibitor, enalapril, in patients with hypertension. We will therefore discuss the possible reason(s) for this low potency, the consequences thereof, and a few therapeutic areas where endothelin-receptor antagonists could find better use.