J-104132

J-104132 (L-753037) is a potent, orally active, selective and competitive ETA/ETB receptor antagonist with K_i of 0.034 nM for ETA and 0.104 nM for ETB receptors. J-104132 inhibits Endothelin-1 (ET-1) (HY-P71446)-induced signaling and vascular contractions in vitro. J-104132 alleviates hypertension, vascular remodeling, and diabetic endothelial dysfunction in vivo by dual ETA/ETB blockade. J-104132 can be used for research on diabetic vascular complications^[1][3]. IC50 & Target:Ki: 0.034 nM (human ET_A receptor, CHO cell), 0.104 nM (human ET_B receptor, CHO cell)^[1] In Vitro:J-104132 potently inhibits ET-1-stimulated phosphatidylinositol hydrolysis (IC₅₀ = 0.059 nM) in human ETA/CHO cells, but fails to stimulate any response by itself at a fully inhibitory concentration (3 nM)^[1].
J-104132 (0.001-10 μM) specifically and competitively antagonizes ET-1-induced contractions in rabbit iliac arteries, as it shifts the ET-1 concentration-response curve rightward without affecting the maximal response and does not inhibit contractions induced by KCl or Norepinephrine (HY-13715)^[1].
J-104132 (3 nM, 20 min) does not change the Ach (HY-B0282)-induced relaxation in diabetic rats aortae^[3]. In Vivo:J-104132 (1, 3, and 10 mg/kg, p.o., single dose) dose-dependently and persistently inhibits the pressor response elicited by big ET-1 in SD rats^[1].
J-104132 (0.1, 0.3 and 1 mg/kg, p.o. or i.v., single dose) dose-dependently inhibits the pressor response elicited by ET-1 in SD rats^[1].
J-104132 (0.01, 0.03, 0.1 and 0.3 mg/kg/h, i.v., infusion for 2 h) shifts ET-1 dose-response curve to the right in a dose-related manner in dogs^[1].
J-104132 (10 mg/kg, i.g., for 2 weeks starting 12 h after balloon injury) decreases the neointima/media ratio in male SD rats and in both male and female ETB-deficient rats, but it has no effect in female wild-type rats^[2].
J-104132 (10 mg/kg, p.o., daily for 4 weeks starting 7 weeks after STZ) restores the impaired acetylcholine (ACh)-induced endothelium-dependent relaxation in Streptozotocin (STZ) (HY-13753)-induced diabetic rats^[3].