Key result
Four small-molecule endothelin receptor antagonists (ABT-627, ABT-546, A-182086, A-192621) exhibited differences in potency and selectivity for ET(A) and ET(B) receptors in vitro.
Why the study?
Do endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621 inhibit ET-1 binding and functional responses in cloned human ET(A) and ET(B) receptors?
Do endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621 inhibit ET-1 binding and functional responses in cloned human ET(A) and ET(B) receptors?
This in vitro study characterizes the potency and selectivity of four small-molecule endothelin receptor antagonists.
Differences among these antagonists may guide preclinical compound selection; leaves open in vivo efficacy and clinical translation.
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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Wu‐Wong et al. (2002) studied this question. Endothelin receptor antagonists (ABT-627, ABT-546, A-182086, A-192621) was evaluated on Inhibition of (125)I-labelled ET-1 binding to cloned human ET(A) and ET(B) receptors, and blocking ET-1-induced functional responses. Four small-molecule endothelin receptor antagonists (ABT-627, ABT-546, A-182086, A-192621) exhibited differences in potency and selectivity for ET(A) and ET(B) receptors in vitro.
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