Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: in vitro studies.

Endothelins (ETs), 21-amino-acid peptides involved in the pathogenesis of various diseases, bind to ET A and ET B receptors to initiate their effects. Based on the same core structure, we have developed four small-molecule ET receptor antagonists, ABT-627, ABT-546, A-182086 and A-192621, which exhibit difference in selectivity for ET A and ET B receptors. In this report, we compare the potency and selectivity of these four antagonists in inhibiting 125 I-labelled ET-1 binding to cloned human ET A and ET B receptors, and in blocking ET-1-induced functional responses (arachidonic acid release and phosphatidylinositol hydrolysis).