A-192621

A-192621 is a potent, nonpeptide, orally active and selective endothelin B (ET_B) receptor antagonist with an IC₅₀ of 4.5 nM and a K_i of 8.8 nM. The selectivity of A-192621 is 636-fold higher than ET_A (IC₅₀ of 4280 nM and K_i of 5600 nM). A-192621 promotes apoptosis in PASMCs. A-192621 alos causes elevation of arterial blood pressure and an elevation in the plasma ET-1 level^[1][2][3]. In Vitro:A-192621 (1-100 μM; 48 hours; PASMCs) treatment markedly reduces the cell viability of PASMCs in a dose-dependent manner^[2].
A-192621 (1-100 μM; 48 hours; PASMCs) treatment significantly increases the caspase-3/7 activity and cleaved caspase-3 expression in PASMCs. A-192621 induces apoptosis in a dose-dependent manner and increases the cells' susceptibility to apoptosis by Doxorubicin treatment^[2].
In Vivo:A-192621 (30-100 mg/kg; oral administration; daily; for 3 days; male Sprague-Dawley rats) treatment inhibits both dilatory and pressor responses induced by S6c mediated by ET_B with an ED₅₀ value of 30 mg/kg, and failed to inhibit the ET-1-induced pressor response mediated by ET_A. A-192621 alone causes elevation of arterial blood pressure and an elevation in the plasma ET-1 level in the conscious normotensive rat^[3].