Endothelin Receptor Antagonist

Bosentan is a competitive and dual antagonist of endothelin-1 (ET) for the ET_A and ET_B receptors with K_i of 4.7 nM and 95 nM in human SMC, respectively.

Ambrisentan is a selective ET type A receptor (ETAR) 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.

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.

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.

BQ-123 is a potent and selective endothelin A (ETA) receptor antagonist with an IC₅₀ of 7.3 nM and a K_i of 25 nM. BQ-123 inhibits endothelin-1-mediated proliferation of human pulmonary artery smooth muscle cells and lowers blood pressure in different rat models of hypertension.

Bosentan hydrate is a competitive and dual antagonist of endothelin-1 (ET) for the ET_A and ET_B receptors with K_i of 4.7 nM and 95 nM in human SMC, respectively.

Sparsentan (RE-021) is a highly potent dual angiotensin II and endothelin A receptor antagonist with K_is of 0.8 and 9.3 nM, respectively.

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.

Atrasentan (ABT-627) is an endothelin receptor antagonist with IC₅₀ of 0.0551 nM for ET_A.

Atrasentan hydrochloride (ABT-627 hydrochloride) is a selective endothelin A receptor antagonist with an IC₅₀ of 0.0551 nM for ET_A.

Clazosentan (Ro 61-1790) is a selective endothelin A (ET_A) receptor antagonist. Clazosentan inhibits ET-1-mediated vasoconstriction. Clazosentan prevents cerebral vasospasm, vasospasm-related cerebral infarction.

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.

Zibotentan (ZD4054) is a potent, selective and orally active endothelin A (ET_A) receptor antagonist with a K_i of 13 nM. Zibotentan has no inhibitory effect on ETB. Zibotentan has anticancer effects and can be used for castration-resistant prostate cancer (CRPC) research.

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).