Key result
IRL 2500 selectively antagonizes endothelin-B receptors to inhibit ET-1 binding and attenuate physiological responses.
Why the study?
A potent and selective ETB receptor antagonist is needed to delineate endothelin responses mediated by the ETB receptor.
Does IRL 2500 inhibit endothelin-B receptor-mediated responses in preclinical models?
Does IRL 2500 inhibit endothelin-B receptor-mediated responses in preclinical models?
IRL 2500 is a potent and selective endothelin-B receptor antagonist that effectively blocks ETB-mediated physiological responses in preclinical models.
IRL 2500 shows potent ETB-selective antagonism in vitro; leaves open any cardiovascular therapeutic role pending in vivo studies.
IRL 2500 [N-(3,5-dimethylbenzoyl)-N-methyl-(D)-(4-phenylphenyl)-alany l-L- tryptophan] inhibited the binding of [125I]-endothelin-1 (ET-1) to human ETB (IC50 1.3 +/- 0.2 nM) and ETA (IC50 94 +/- 3 nM) receptors expressed in transfected Chinese hamster ovary (CHO) cells. In in vitro studies, IRL 2500 inhibited the sarafotoxin S6c (STX6c)-mediated contraction of the dog saphenous vein (pKb 7.77) and the STX6c-induced relaxation of the preconstricted rabbit mesenteric artery (pKb 6.92). In the anesthetized rat, IRL 2500 (10 mg/kg, i.v.) inhibited the initial transient decrease in mean arterial pressure (MAP) induced by the ETB-selective agonist IRL 1620 (0.5 nmol/kg, i.v.). IRL 2500 also attenuated the IRL 1620-mediated increase in renal vascular resistance (RVR) in the anesthetized rat. Therefore, IRL 2500 is a potent and selective ETB receptor antagonist that can be used to delineate ET responses mediated by the ETB receptor.
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Balwierczak et al. (1995) studied this question. IRL 2500 was evaluated on Binding of [125I]-endothelin-1 to human ETB and ETA receptors and physiological responses in animal models. IRL 2500 is a potent and selective endothelin-B receptor antagonist that inhibited ET-1 binding (IC50 1.3 nM for ETB) and attenuated ETB-mediated physiological responses in vitro and in vivo.
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