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Macitentan

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Chemical Structure| 441798-33-0 同义名 : ACT-064992;Actelion-1;brand name: Opsumit.
CAS号 : 441798-33-0
货号 : A539182
分子式 : C19H20Br2N6O4S
纯度 : 98%
分子量 : 588.273
MDL号 : MFCD17167076
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(84.99 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
动物实验配方：
生物活性
靶点

  • ET-A

    ET-A, IC50:0.5 nM

  • ET-B

    ET-B, IC50:391 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[5]. The three structurally closely related peptides, named endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3), are among the most potent vasoconstrictors known in humans. They convey their action through binding to two G-protein coupled receptors called ETA and ETB. Among the three isopeptides, ET-1 appears to be the key player in the cardiovascular system. ET-2 and ET-3 are specifically expressed in the gastrointestinal tract and the brain, respectively. Macitentan is a dual ETA/ETB receptors antagonist designed through a deliberate discovery process to maximize endothelin-axis blockade while improving adverse-effect profiles with IC50 of 0.5 nM and 391 nM for ETA and ETB, respectively. Macitentan is a dual endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH). The physicochemical properties of macitentan favor penetration into lung tissue, where macitentan predominantly exerts its effects. Macitentan is highly bound to plasma proteins. In a vivo experiment, Macitentan treatment at 1 mg/kg/day for five consecutive days stably reduced mean arterial blood pressure by -20 mmHg over the whole treatment period and made it returned to baseline about 48h after the last dose was given in Dahl salt-sensitive rats[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.70mL

0.34mL

0.17mL

8.50mL

1.70mL

0.85mL

17.00mL

3.40mL

1.70mL
参考文献

[1]Sen S, Chen S, et al. Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist. Life Sci. 2012 Oct 15;91(13-14):658-68.

[2]Iglarz M, Binkert C, et al. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. J Pharmacol Exp Ther. 2008 Dec;327(3):736-45.

[4]The Discovery of N‑[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]‑N′‑propylsulfamide (Macitentan), an Orally Active, Potent Dual Endothelin Receptor Antagonist

[5]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.