1. GPCR/G Protein
  2. Prostaglandin Receptor

NS-304 (Synonyms: Selexipag; ACT-293987)

Cat. No.: HY-14870 Purity: 99.97%
Data Sheet SDS Handling Instructions

NS-304 is an orally available and potent agonist for the Prostacyclin (PGI2) receptor (IP receptor).

For research use only. We do not sell to patients.
NS-304 Chemical Structure

NS-304 Chemical Structure

CAS No. : 475086-01-2

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $105 In-stock
5 mg $95 In-stock
10 mg $145 In-stock
50 mg $480 In-stock
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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

NS-304 is an orally available and potent agonist for the Prostacyclin (PGI2) receptor (IP receptor).

IC50 & Target

Prostacyclin receptor[1]

In Vitro

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. 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 NS-304 with EC50 of 177nM. 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].

In Vivo

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. 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, 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].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT00993408 Actelion Pulmonary Arterial Hypertension April 2008 Phase 2
NCT01112306 Actelion Pulmonary Arterial Hypertension December 2009 Phase 3
NCT00993408 Actelion Pulmonary Arterial Hypertension April 2008 Phase 2
NCT01112306 Actelion Pulmonary Arterial Hypertension December 2009 Phase 3
NCT02882425 Actelion Healthy Subjects January 2015 Phase 1
NCT02745860 Actelion Healthy Subjects June 2016 Phase 1
NCT03187678 Actelion Pulmonary Arterial Hypertension July 31, 2017 Phase 3
NCT02791815 Actelion Healthy Subjects July 2016 Phase 1
NCT02260557 Actelion Raynaud's Phenomenon Secondary to Systemic Sclerosis October 2014 Phase 2
NCT02206295 Actelion Bioequivalence September 2012 Phase 1
NCT02770222 Actelion Healthy Subjects June 2016 Phase 1
NCT02471183 Actelion Pulmonary Arterial Hypertension November 4, 2015 Phase 3
NCT03078907 Actelion Pulmonary Arterial Hypertension August 31, 2017 Phase 4
NCT01106014 Actelion Pulmonary Arterial Hypertension December 2009 Phase 3
NCT02206204 Actelion Cardiodynamics|Safety|Tolerability|Pharmacokinetics June 2012 Phase 1
NCT02558231 Actelion Pulmonary Arterial Hypertension May 2016 Phase 3
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.0136 mL 10.0681 mL 20.1361 mL
5 mM 0.4027 mL 2.0136 mL 4.0272 mL
10 mM 0.2014 mL 1.0068 mL 2.0136 mL
Cell Assay
[1]

NS-304 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1].

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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

NS-304 is prepared in aqueous solution[1].

Mice[1]
Male Sprague-Dawley rats, cynomolgus monkeys, and male beagle dogs are used. S-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 NS-304 and MRE-269 after oral administration of 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 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 NS-304 at 3 mg/kg. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

496.62

Formula

C₂₆H₃₂N₄O₄S

CAS No.

475086-01-2

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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NS-304
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