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Bosentan hydrate

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Chemical Structure| 157212-55-0 同义名 : 波生坦 一水合物 ;Ro 47-0203
CAS号 : 157212-55-0
货号 : A404664
分子式 : C27H31N5O7S
纯度 : 98%
分子量 : 569.629
MDL号 : MFCD09751188
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(184.33 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 50 mg/mL(87.78 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

2% DMSO+30% PEG 300+2% Tween 80+water 5 mg/mL

生物活性
靶点

  • ET-A

    ET-A, Ki:4.7 nM

  • ET-B

    ET-B, Ki:95 nM
描述 G protein-coupled receptor (GPCR) agonists through their receptors can transactivate protein tyrosine kinase receptors such as epidermal growth factor receptor and serine/threonine kinase receptors most notably transforming growth factor (TGF)‐β receptor (TβRI). Several GPCR agonists such as Ang II, thrombin, ET-1 can mediate the transactivation of a multitude of protein tyrosine kinase receptors[3]. Endothelin (ET) is an endothelium-derived 21-residue vasoconstrictor peptide. The ETs have three distinct isoforms, namely ET-1, ET-2, and ET-3. ET-1 is the most abundant isoform and the best characterized in vivo, and it is the only one that is constitutively released by the vascular endothelium[4]. Bosentan hydrate (BST) is a competitive dual endothelin receptor antagonist that is nonselective for both endothelin A and endothelin B receptors with a Ki of 4.1 - 4.7 nM[5]. It decreases both pulmonary vascular resistance and systemic vascular resistance and hence increases cardiac output without increasing the heart rate[6]. In a vivo study, the rats were intragastrically administered with 100 mg/kg bosentan half an hour after Paraquat exposure, and then once a day. After bosentan administration, the ET-1 and TGF-β1 content of the serum and lungs gradually decreased and were markedly lower than in the Paraquat group on the 21st day which indicated that early treatment with bosentan after Paraquat poisoning may be helpful in ameliorating lung injury and decreasing lung fibrosis[4]. In a study, bosentan was given orally (1000 mg b.i.d.) for 14 days to patients who were also being treated for chronic heart failure (CHF) with digitalis, angiotensin-converting enzyme inhibitors (ACEIs) and diuretics and the results demonstrated that addition of bosentan to ongoing therapy for patients with CHF reduced systemic and pulmonary vascular resistance and increased cardiac index, without affecting heart rate. Bosentan treatment of patients with CHF already receiving ACEIs and diuretics significantly decreased plasma aldosterone levels[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.76mL

0.35mL

0.18mL

8.78mL

1.76mL

0.88mL

17.56mL

3.51mL

1.76mL
参考文献

[1]Ostrowski RP, Januszewski S, et al. Effect of endothelin receptor antagonist bosentan on plasma leptin concentration in acute myocardial infarction in rats. Pathophysiology. 2003 Sep;9(4):249-256.

[2]Clozel M, Breu V, et al. Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist. J Pharmacol Exp Ther. 1994 Jul;270(1):228-35.

[3]Sharifat N, Mohammad Zadeh G, Ghaffari MA, Dayati P, Kamato D, Little PJ, Babaahmadi-Rezaei H. Endothelin-1 (ET-1) stimulates carboxy terminal Smad2 phosphorylation in vascular endothelial cells by a mechanism dependent on ET receptors and de novo protein synthesis. J Pharm Pharmacol. 2017 Jan;69(1):66-72. doi: 10.1111/jphp.12654. Epub 2016 Dec 1. PMID: 27905105.

[4]Zhang Z, Jian X, Zhang W, Wang J, Zhou Q. Using bosentan to treat paraquat poisoning-induced acute lung injury in rats. PLoS One. 2013 Oct 14;8(10):e75943. doi: 10.1371/journal.pone.0075943. PMID: 24155875; PMCID: PMC3796527.

[5]Rubin LJ, Roux S. Bosentan: a dual endothelin receptor antagonist. Expert Opin Investig Drugs. 2002 Jul;11(7):991-1002. doi: 10.1517/13543784.11.7.991. PMID: 12084009.

[6]Lee HJ, Kang JH, Lee HG, Kim DW, Rhee YS, Kim JY, Park ES, Park CW. Preparation and physicochemical characterization of spray-dried and jet-milled microparticles containing bosentan hydrate for dry powder inhalation aerosols. Drug Des Devel Ther. 2016 Dec 13;10:4017-4030. doi: 10.2147/DDDT.S120356. PMID: 28008226; PMCID: PMC5167478.