ET_B Antagonist

Macitentan (ACT-064992) is an orally active, non-peptide dual ETA and ETB (endothelin receptor) antagonist. Macitentan has the potential for idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).

BQ-788 is a potent, selective ETB receptor antagonist with IC₅₀ of 1.2 nM for inhibition of ET-1 binding to human Girardi heart cells, poorly inhibiting the binding to ETA receptors in human neuroblastoma cell line SK-N-MC cells with IC₅₀ of 1300 nM.

Aprocitentan (ACT-132577) is the major and pharmacologically active metabolite of Macitentan. Aprocitentan is an orally active dual ETA/ETB antagonist with IC₅₀s of 3.4 nM and 987 nM, and pA₂ valus of 6.7 and 5.5, respectively. Aprocitentan is an antihypertensive agent.

Sitaxsentan sodium (IPI 1040 sodium; TBC11251 sodium) is a potent, selective and orally active endothelin A receptor (ETA) antagonist with an IC₅₀ of 1.4 nM and a K_i of 0.43 nM. Sitaxsentan sodium exhibits an IC₅₀ for the ETB receptor of as high as 9800 nM. Sitaxsentan sodium is metabolized by CYP2C9 and CYP3A4, normalizes shunt-induced endothelial abnormalities, restores BMPR signaling, and suppresses pulmonary vascular remodeling and hemodynamic deterioration. Sitaxsentan sodium can be applied in the research of pulmonary arterial hypertension and portopulmonary hypertension.

PD151242 is a selective competitive antagonist of the endothelin ET_A receptor, with K_D values of 0.65 nM, 0.64 nM and 1.92 nM for human, rat and porcine receptors, respectively, and a K_D value of 104 μM for the human ET_β receptor. When radiolabeled as [¹²⁵I]-PD151242, PD151242 can be used to visualize and localize renal vascular ET_A receptors.

BQ-788 sodium salt is a potent and selective ETB receptor antagonist, inhibiting ET-1 binding to ETB receptors with an IC₅₀ of 1.2 nM in human Girrardi heart cells.

Sulfisoxazole (Sulfafurazole) is an orally active endothelin receptor antagonist with IC₅₀ values of 0.60 μM and 22 μM against endothelin receptor A and endothelin receptor B, respectively. Sulfisoxazole is a sulfonamide antibacterial agent with an oxazole substituent. Sulfisoxazole inhibits breast cancer exosome release by targeting endothelin receptor A.

Tezosentan (RO 610612) is an endothelin (ET) receptor antagonist, with pA₂s of 9.5, 7.7 for ET_A and ET_B receptors, respectively.

IRL 2500 is a potent Endothelin receptor antagonist. IRL 2500 shows IC₅₀ values of 1.3 and 94 nM for ET_B and ET_A receptors, respectively. IRL 2500 inhibits ETB receptor-mediated blood pressure increase and renal vascular resistance in rats in vivo.

A-192621, a chemical probe, 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.

Macitentan-d₄ is a deuterium labeled Sulfamethoxazole. Macitentan is an orally active, non-peptide dual ETA and ETB (endothelin) receptor antagonist. Macitentan has the potential for idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).

Aprocitentan-d₄ is a deuterium labeled Aprocitentan. Aprocitentan is a major and pharmacologically active metabolite of Macitentan. Aprocitentan is an orally active dual ETA/ETB antagonist with IC50s of 3.4 nM and 987 nM, and pA2 valus of 6.7 and 5.5, respectively. Aprocitentan is an antihypertensive agent.

Ro 46-8443 is the first non-peptide endothelin ET_B receptor selective antagonist. Ro 46-8443 displays an at least 100-fold selectivity for ET_B (IC₅₀: 34-69 nM) over ET_A receptors (IC₅₀: 6800 nM).

Nebentan (YM598 free base) is a potent, selective and orally active non-peptide endothelin ET_A receptor antagonist through the modification of Bosentan (HY-A0013). Nebentan inhibits [¹²⁵I] endothelin-1 binding to cloned human endothelin ETA and ETB receptor, with K_i of 0.697 nM and 569 nM, respectively. YM598 can ameliorate the progression of cor pulmonale and myocardial infarction in vivo.

Nebentan potassium (YM598) is a potent, selective and orally active non-peptide endothelin ET_A receptor antagonist through the modification of Bosentan (HY-A0013). Nebentan potassium inhibits [¹²⁵I] endothelin-1 binding to cloned human endothelin ETA and ETB receptor, with K_i of 0.697 nM and 569 nM, respectively. YM598 can ameliorate the progression of cor pulmonale and myocardial infarction in vivo.

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].

Edonentan (BMS 207940) is an orally active, highly selective endothelin A receptor (ET_A receptor) antagonist with a K_i value of 0.01 nM against human targets. Edonentan blocks the pressor response induced by Big Endothelin-1 in conscious normotensive rats and the pressor response induced by ET-1 in conscious normotensive cynomolgus monkeys. Edonentan can be used in research related to cardiovascular diseases.

Sitaxsentan (IPI 1040 sodium; TBC11251 sodium) is a potent, selective and orally active endothelin A receptor (ETA) antagonist with an IC₅₀ of 1.4 nM and a K_i of 0.43 nM. Sitaxsentan exhibits an IC₅₀ for the ETB receptor of as high as 9800 nM. Sitaxsentan is metabolized by CYP2C9 and CYP3A4, normalizes shunt-induced endothelial abnormalities, restores BMPR signaling, and suppresses pulmonary vascular remodeling and hemodynamic deterioration. Sitaxsentan can be applied in the research of pulmonary arterial hypertension and portopulmonary hypertension.

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.

BMS-193884 is a selective, orally active, and competitive ET_A antagonist with 10000-fold greater affinity for the human ET_A receptor (K_i=1.4 nM) than for the ET_B receptor.