NS 304 (Synonyms: ACT293987, Selexipag) |
Catalog No.GC16639
One-Click Copy Product Info
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NS 304 (NS-304) is an orally available and potent agonist for the Prostacyclin (PGI2) receptor (IP receptor).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 475086-01-2
Sample solution is provided at 25 µL, 10mM.
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Selexipag (NS-304) is an orally available and potent agonist for the Prostacyclin (PGI2) receptor (IP receptor).
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 receptor. Selexipag (NS-304) inhibits the binding of [3H]Iloprost to the human and rat IP receptors in a concentration-dependent manner. The Ki is 260 nM for the human IP receptor and 2100 nM for the rat IP receptor. The intracellular cAMP levels in hIP-CHO cells are increased in a concentration-dependent manner 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 μM, respectively, but it shows no inhibition in dogs (IC50 of >100 μM)[1].
The Cmax of MRE-269 after oral administration of NS-304 is 1.1 μg/mL in rats and 9.0 μg/mL in dogs. Selexipag (NS-304) at 1 or 3 mg/kg increases FSBF in anesthetized rats for more than 4 h after intraduodenal administration in a dose-dependent manner. In particular, Selexipag (NS-304) at 3 mg/kg causes a sustained increase in FSBF and exhibits a maximal increase of 93% in FSBF 1 h after administration[1].
References:
[1]. Kuwano K, et al. 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-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, selexipag's active compound, at the pseudoglandular stage improves lung vasculature. Am J Physiol Lung Cell Mol Physiol. 2018 May 10.
Cell experiment: | CHO cells expressing the human IP receptor (hIP-CHO cells) are seeded at 1×105 cells/well in a 24-well plate and cultured for 48 h. The cells are washed with Dulbecco's phosphate-buffered saline without divalent cations, preincubated in the medium for 1 h at 37°C, and then incubated for 15 min at 37°C with medium containing each drug in the presence of 500 μM 3-isobutyl-1-methylxanthine. The medium is removed, and perchloric acid solution is added to terminate the reaction. Intracellular cAMP levels are measured by enzymelinked immunosorbent assay[1]. |
Animal experiment: | Mice[1] Male Sprague-Dawley rats, cynomolgus monkeys, and male beagle dogs are used. Selexipag (NS-304) is orally administered to rats at 10 mg/kg and to dogs at 3 mg/kg, and blood samples are collected at various times and centrifuged to obtain plasma. The plasma concentrations of Selexipag (NS-304) and MRE-269 after oral administration of Selexipag (NS-304) to each animal are determined by high performance liquid chromatography coupled to mass spectrometry (LC/MS), and their pharmacokinetic parameters are calculated.Rats are orally administered Selexipag (NS-304) at 3 mg/kg twice daily for 1, 2, 3, or 4 weeks as a pretreatment. On the day after the final administration in the pretreatment, rats are anesthetized with urethane, and the FSBF is measured with a laser Doppler flowmeter after intraduodenal administration of Selexipag (NS-304) at 3 mg/kg[1]. |
References: [1]. Kuwano K, et al. 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther. 2007 Sep;322(3):1181-8. | |
| Cas No. | 475086-01-2 | SDF | |
| Synonyms | ACT293987, Selexipag | ||
| Chemical Name | 2-(4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)-N-(methylsulfonyl)acetamide | ||
| Canonical SMILES | O=C(COCCCCN(C1=NC(C2=CC=CC=C2)=C(C3=CC=CC=C3)N=C1)C(C)C)NS(=O)(C)=O | ||
| Formula | C26H32N4O4S | M.Wt | 496.62 |
| Solubility | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 50 mg/ml,PBS (pH 7.2): 1 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0136 mL | 10.0681 mL | 20.1361 mL |
| 5 mM | 402.7 μL | 2.0136 mL | 4.0272 mL |
| 10 mM | 201.4 μL | 1.0068 mL | 2.0136 mL |
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 39 reference(s) in Google Scholar.)