PD-156707

PD-156707 is an orally active, nonpeptide and selective Endothelin-A receptor antagonist. PD-156707 binds to human ET-A and ET-B receptors with K_i values of 0.17 nM and 133.8 nM, respectively. PD-156707 shows reversal of established chronic hypoxic pulmonary hypertension in rats. PD-156707 can be used for the study of diseases associated with abnormal ET-A receptor activation, particularly pulmonary hypertension, stroke, and heart failure^[1][2]. In Vitro:PD-156707 inhibits inositol phosphate production induced by ET-1 in Ltk cells (IC₅₀ = 2.4 nM) and arachidonic acid release stimulated by ET-1 in rabbit renal artery VSMC cells (IC₅₀ = 1.1 nM)^[1].
PD-156707 (0.1-10 μM) cause a rightward shift in the concentration-response curve of ET-1-stimulated contraction of rabbit femoral artery^[1].
PD-156707 (1 μM) exerts a significant inhibitory effect on spontaneous neointimal proliferation of transverse sections of human saphenous vein^[1].
In Vivo:PD-156707 (10-40 mg/kg, p.o., daily) shows dose-related reversal of established chronic hypoxic pulmonary hypertension and attenuation of right ventricular hypertrophy in rats^[1].
PD-156707 (0.003-0.3 mg/kg/h, i.v. infusion, 1 h) shows dose-dependent inhibition of ET-1-induced renal vascular resistance (RVR) increase in rabbits^[2].