A-192621 is a potent, nonpeptide, orally active, and selective endothelin B (ETB) receptor antagonist with an IC50 of 4.5 nM and a Ki of 8.8 nM. A-192621 promotes apoptosis in PASMCs and elevates both arterial blood pressure and plasma ET-1 levels[1][2][3]. Its selectivity is 636-fold higher for ETB than ETA (IC50 of 4280 nM and Ki of 5600 nM).

ETB:4.5 nM, ETB:8.8 nM （ki）, ETA:4280 nM, ETA:5600 nM （ki）

A-192621 induces apoptosis in a dose-dependent manner and increases the cells' susceptibility to apoptosis by Doxorubicin treatment[2]. A-192621 (1-100 μM; 48 hours; PASMCs) treatment markedly reduces the cell viability of PASMCs in a dose-dependent manner[2] and it treatment significantly increases the caspase-3/7 activity and cleaved caspase-3 expression in PASMCs.

A-192621 (30-100 mg/kg; oral administration; daily; for 3 days; male Sprague-Dawley rats) inhibits dilatory and pressor responses induced by S6c mediated by ETB, with an ED50 of 30 mg/kg, but fails to inhibit the ET-1-induced pressor response mediated by ETA. A-192621 alone raises arterial blood pressure and plasma ET-1 levels in the conscious normotensive rat[3].