Selexipag-NS-304-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESelexipagCat. No.: HY-14870CAS No.: 475086-01-2Synonyms: NS-304; ACT-293987分式: CHNOS分量: 496.62作靶点: Prostaglandin Receptor作通路: GPCR/G Protein储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 5

2、0 mg/mL (100.68 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.03 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.03 mM); Suspended solution; Need ultrasonic3. 请依序添加每种溶剂： 10% DMSO 90% co

3、rn oilSolubility: 2.5 mg/mL (5.03 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Selexipag (NS-304)种服有效的 前列环素 (PGI2) 受体激动剂。IC50 & Target IP Receptor体外研究 Selexipag (NS-304) is an orally available and long-acting IP receptor agonist prodrug, and its active form,MRE-269, is highly selective for the IP recep

4、tor. Selexipag (NS-304) inhibits the binding of 3HIloprost to thehuman and rat IP receptors in a concentration-dependent manner. The Ki is 260 nM for the human IPreceptor and 2100 nM for the rat IP receptor. The intracellular cAMP levels in hIP-CHO cells are increased ina concentration-dependent man

5、ner by treatment with Selexipag (NS-304) with EC50 of 177nM. Selexipag(NS-304) also inhibits platelet aggregation in humans and monkeys with IC50 values of 5.5 and 3.4 M,respectively, but it shows no inhibition in dogs (IC50 of 100 M) 1.体内研究 The Cmax of MRE-269 after oral administration of NS-304 is

6、 1.1 g/mL in rats and 9.0 g/mL in dogs.Selexipag (NS-304) at 1 or 3 mg/kg increases FSBF in anesthetized rats for more than 4 h afterintraduodenal administration in a dose-dependent manner. In particular, Selexipag (NS-304) at 3 mg/kgcauses a sustained increase in FSBF and exhibits a maximal increas

7、e of 93% in FSBF 1 h afteradministration 1.PROTOCOLCell Assay 1 CHO cells expressing the human IP receptor (hIP-CHO cells) are seeded at 1105 cells/well in a 24-wellplate and cultured for 48 h. The cells are washed with Dulbeccos phosphate-buffered saline without divalentcations, preincubated in the

8、 medium for 1 h at 37C, and then incubated for 15 min at 37C with mediumcontaining each drug in the presence of 500 M 3-isobutyl-1-methylxanthine. The medium is removed, andperchloric acid solution is added to terminate the reaction. Intracellular cAMP levels are measured byenzymelinked immunosorben

9、t assay 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Male Sprague-Dawley rats, cynomolgus monkeys, and male beagle dogs are used. Selexipag (NS-304) isorally administered to rats at 10 mg/kg and to dogs at 3 mg/kg, and

10、 blood samples are collected at varioustimes and centrifuged to obtain plasma. The plasma concentrations of Selexipag (NS-304) and MRE-269after oral administration of Selexipag (NS-304) to each animal are determined by high performance liquidchromatography coupled to mass spectrometry (LC/MS), and t

11、heir pharmacokinetic parameters arecalculated.Rats are orally administered Selexipag (NS-304) at 3 mg/kg twice daily for 1, 2, 3, or 4 weeks as apretreatment. On the day after the final administration in the pretreatment, rats are anesthetized with2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEure

12、thane, and the FSBF is measured with a laser Doppler flowmeter after intraduodenal administration ofSelexipag (NS-304) at 3 mg/kg 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Am J Physiol Lung Cell Mol Physiol. 2018 Aug 1;315(2):L276-L2

13、85. Erasmus Universiteit Rotterdam. 2017, November 30.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Kuwano K, et al. 2-4-(5,6-diphenylpyrazin-2-yl)(isopropyl)aminobutoxy-N-(methylsulfonyl)acetamide (NS-304), an orally available andlong-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther. 2007 Sep;322(3):1181-8.2. Mous DS, et al. Treatment of rat congenital diaphragmatic hernia with sildenafil and NS-304, selexipags active compound, at thepseudoglandular stage improves lung vasculature. Am J Physiol Lung Cell Mol Physiol. 2018