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

  • Clin Sci (Lond). 2002 Aug;103 Suppl 48:107S-111S. doi: 10.1042/CS103S107S.
J Ruth Wu-Wong  1 ,  Douglas B Dixon ,  William J Chiou ,  Brian K Sorensen ,  Gang Liu ,  H-S Jae ,  Andrew Tasker ,  Thomas W von Geldern ,  Martin Winn ,  Terry J Opgenorth
Affiliations
  • 1. Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, U.S.A. [email protected]
PMID: 12193066 DOI: 10.1042/CS103S107S
Abstract

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).

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