endothelin-1 receptor

Aminaftone, a derivative of 4-aminobenzoic acid, inhibits endothelin-1 (ET-1) production and is used to study hypertension and systemic sclerosis.

Atrial Natriuretic Peptide (ANP) (1-28), human, porcine Acetate is an atrial natriuretic peptide (ANP) hormone secreted by atrial myocytes that is capable of acting as an natriuretic peptide receptor-A(NPR-A) agonist, used in the treatment of acute decompensated heart failure (ADHF). By binding to specific receptors on the surface of the kidney, blood vessel, and heart cells, Carperitide causes an increase in cyclic guanosine monophosphate (cGMP) levels and induces vasodilatation, diuresis, and sodium excretion, which in turn reduces the heart's workload.

Clazosentan (Ro 61-1790) is a selective antagonist of the endothelin A receptor (ETAreceptor) that inhibits ET-1-mediated vasoconstriction, preventing cerebral vasospasm and vasospasm-associated cerebral infarction.

Avosentan(Ro 67-0565; SPP-301) is a potent endothelin receptor (ETA) antagonist with strong inhibitory effects on endothelin-1-induced contraction and may have protective effects against chronic kidney disease. [2]

Sacubitril hemicalcium salt (AHU377 calcium salt) is a potent NEP inhibitor with an IC50 of 5 nM. Sacubitril hemicalcium salt is a component of the heart failure medicine LCZ696. Sacubitril hemicalcium salt is a prodrug of LBQ657, which is an inhibitor of the zinc metallopeptidase neprilysin. Neprilysin degrades a variety of vasoactive peptides such as atrial and brain natriuretic peptide, bradykinin, adrenomedullin, and endothelin-1. Inhibition of neprilysin leads to an increased level of these peptides and, thus, antihypertensive effects. Formulations containing AHU377 in combination with the angiotensin II receptor antagonist valsartan are used to treat hypertension and heart failure.

Bosentan (Benzenesulfonamide) is a sulfonamide-derived, competitive and specific endothelin receptor antagonist with a slightly higher affinity for the endothelin A receptor than endothelin B receptor. Bosentan blocks the action of endothelin 1, an extremely potent endogenous vasoconstrictor and bronchoconstrictor, by binding to endothelin A and endothelin B receptors in the endothelium and vascular smooth muscle. Bosentan decreases both pulmonary and systemic vascular resistance and is particularly used in the treatment of pulmonary arterial hypertension.

Selective and competitive urotensin-II (UT) receptor antagonist (pKB = 8.3). Blocks hU-II induced contractions in thoracic aorta ex vivo. Exhibits no effect on noradrenaline or endothelin 1-induced contraction or on acetylcholine-induced relaxation. Behav

ABT-546 (A-216546) is a potent, highly selective, and active endothelin ETA receptor antagonist with a Ki of 0.46 nM for [125I]endothelin-1 binding to cloned human endothelin ETA.

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).

BMS-248360 is a potent, orally active dual antagonist of both angiotensin II receptor (AT1) and endothelin A (ETA) receptor, with Kis of 10 nM and 1.9 nM for hAT1 and hETA receptors, respectively. BMS-248360 demonstrates hypertensive effects[1].

TBC3711 is an endothelin receptor modulator. It is used for the research of endothelin-mediated disorders.

IRL-1620 acetate is an effective and selective agonist of Endothelin B receptor (ETB) with a Ki of 16 pM which is more selective than ETA with a Ki of 19 μM.

Endothelin 1 (swine, human), a synthetic peptide mirroring the sequence of both human and swine Endothelin 1, functions as a robust endogenous vasoconstrictor by interacting with two receptor types, ETA and ETB.

Endothelin 1 (swine, human) acetate is a synthetic peptide with the sequence of human and swine Endothelin 1. Endothelin 1 is a potent endogenous vasoconstrictor and acts through two types of receptors ETA and ETB.

CYM5442 is an S1P agonist, targeting to Sphingosine.

ENDOTHELIN-1 (ET-1), the principal peptide of the endothelin family, has been shown to have a variety of biological activities in both vascular and nonvascular tissues. The C-terminal fragment, which is a highly conserved sequence in the peptides of t

Ac-Endothelin-1 (16-21), human acetate, the principal peptide of the endothelin family, has been shown to have a variety of biological activities in both vascular and nonvascular tissues. The C-terminal fragment, which is a highly conserved sequence in th

J-104132 is a potetn and selective endothelin A/B receptor antagonist (Ki: cloned human ETA = 0.034 nM; cloned human ETB = 0.104 nM) . In vitro, J-104132 is a potent antagonist of ET-1-induced accumulation of [3H]inositol phosphates in Chinese hamster ova

Ro 46-2005 is a synthetic non-peptide endothelin receptor antagonist, inhibits the specific binding of 125I-ET-1 to human vascular smooth muscle cells (ETA receptor, IC50: 220 nM).

ACT-373898 is a metabolite of the endothelin (ET) receptor type A (ETA) and ETBdual antagonist macitentan .1 1.Dingemanse, J., Sidharta, P.N., Maddrey, W.C., et al.Efficacy, safety and clinical pharmacology of macitentan in comparison to other endothelin receptor antagonists in the treatment of pulmonary arterial hypertensionExpert Opin. Drug Saf.13(3)391-405(2013)

Nebentan (YM598) is a potent, selective and orally active non-peptide endothelin ETA receptor antagonist through the modification of Bosentan . Nebentan inhibits [125I] endothelin-1 binding to cloned human endothelin ETA and ETB receptor, with Ki of 0.697 nM and 569 nM, respectively[1]. YM598 can ameliorate the progression of cor pulmonale and myocardial infarction in vivo[2]. Nebentan inhibits the specific binding of [125I] endothelin-1 to endothelin ETA and ETB receptors in a concentration dependent manner,Ki values are 0.697 nM and 1.53 nM for human and rat endothelin ETA receptors, respectively. In contrast, YM598 exhibits low affinities for human and rat endothelin ETB receptors, with Ki values of 569 nM and 155 nM,respectively[1].In measurement of intracellular Ca2+ concentration, Nebentan concentration-dependently inhibits the increase in [Ca2+]i induced by 10 nM endothelin-1 in both CHO cells and A10 cells, the IC50 values are 26.2 nM for CHO cells and 26.7 nM for A10 cells, respectively[1]. Nebentan (oral administration; 0.1-1 mg/kg; 4 weeks) significantly inhibits the progression of pulmonary hypertension and the development of right ventricular hypertrophy[2].Nebentan (oral administration; 1 mg/kg; 30 weeks) significantly ameliorates the poor survival rate of CHF rats, it markedly reduces the hypertrophy of both ventricles as well as pulmonary congestion[2]. [1]. Hironori Yuyama, et al. Pharmacological Characterization of YM598, an Orally Active and Highly Potent Selective Endothelin ET(A) Receptor Antagonist. Eur J Pharmacol. 2003 Sep 30;478(1):61-71. [2]. Akira Fujimori, et al. YM598, an Orally Active ET(A) Receptor Antagonist, Ameliorates the Progression of Cardiopulmonary Changes and Both-Side Heart Failure in Rats With Cor Pulmonale and Myocardial Infarction. J Cardiovasc Pharmacol. 2004 Nov;44 Suppl 1:S354-7.

Thrombin receptor agonist peptide (TRAP-14) is a 14-amino acid peptide agonist of the α-thrombin receptor. It induces aggregation of washed platelets as well as platelets in citrated and hirudin plasma. TRAP-14 (100 μM) increases the cytosolic calcium concentration in isolated guinea pig pulmonary smooth muscle cells 5-fold over baseline. It increases pulmonary arterial pressure in isolated guinea pig lung when used at a concentration of 1 μM, which is comparable to the effect induced by 10 nM α-thrombin. TRAP-14 also induces contraction of isolated rat aortic rings and increases endothelin-1 (ET-1) levels in a dose-dependent manner, an effect that is reversed by the ETA antagonist BQ-123 and the nitric oxide synthase (NOS) inhibitor L-NNA .

Desmethyl bosentan, an active metabolite of the endothelin receptor antagonist bosentan, activates the pregnane X receptor (PXR) in CV-1 monkey kidney cells expressing the human receptor in a reporter assay at a concentration of 25 μM.

BE-24566B is a polyketide fungal metabolite originally isolated fromS. violaceusniger.1It is active againstB. subtilis,B. cereus,S. aureus,M. luteus,E. faecalis, andS. thermophilus(MICs = 1.56, 1.56, 1.56, 1.56, 3.13, and 3.13 μg/ml, respectively). BE-24566B is an endothelin (ET) receptor antagonist (IC50s = 11 and 3.9 μM for ETAand ETBreceptors, respectively).2 1.Kojiri, K., Nakajima, S., Fuse, A., et al.BE-24566B, a new antibiotic produced by Streptomyces violaceusnigerJ. Antibiot. (Tokyo)48(12)1506-1508(1995) 2.Lam, Y.K.T., Hensens, O., Helms, G., et al.L-755,805, a new polyketide endothelin binding inhibitor from an actinomyceteTetrahedron Lett.36(12)2013-2016(1995)