Selexipag
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MedKoo CAT#: 317125

CAS#: 475086-01-2

Description: Selexipag, also known as ACT-293987 and NS-304, is a a first-in-class orally available selective non-prostanoid IP receptor agonist, which is currently in development by Actelion as a treatment of pulmonary arterial hypertension. Selexipag and its active metabolite, ACT-333679, are agonists at the prostacyclin receptor, which leads to vasodilation in the pulmonary circulation.


Chemical Structure

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Selexipag
CAS# 475086-01-2

Theoretical Analysis

MedKoo Cat#: 317125
Name: Selexipag
CAS#: 475086-01-2
Chemical Formula: C26H32N4O4S
Exact Mass: 496.21
Molecular Weight: 496.620
Elemental Analysis: C, 62.88; H, 6.50; N, 11.28; O, 12.89; S, 6.46

Price and Availability

Size Price Availability Quantity
25mg USD 90 Ready to ship
50mg USD 150 Ready to ship
100mg USD 250 Ready to ship
200mg USD 450 Ready to ship
500mg USD 950 Ready to ship
1g USD 1650 Ready to ship
2g USD 2950 Ready to ship
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Synonym: NS-304; NS304; NS 304; ACT-293987; ACT293987; ACT 293987; Selexipag; Uptravi.

IUPAC/Chemical Name: 2-{4-[(5,6-diphenylpyrazin-2-yl)(propan-2-yl)amino]butoxy}-N-(methanesulfonyl)acetamide

InChi Key: QXWZQTURMXZVHJ-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H32N4O4S/c1-20(2)30(16-10-11-17-34-19-24(31)29-35(3,32)33)23-18-27-25(21-12-6-4-7-13-21)26(28-23)22-14-8-5-9-15-22/h4-9,12-15,18,20H,10-11,16-17,19H2,1-3H3,(H,29,31)

SMILES Code: CC(N(CCCCOCC(NS(C)(=O)=O)=O)C1=NC(C2=CC=CC=C2)=C(C3=CC=CC=C3)N=C1)C

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Selexipag (NS-304) is an agonist for the Prostacyclin (PGI2) receptor (IP receptor) with Ki of 260 nM.
In vitro activity: Prostacyclin (PGI2) receptor (IP receptor) agonists, which are indicated for the treatment of pulmonary arterial hypertension (PAH), increase cytosolic cAMP levels and thereby inhibit pulmonary vasoconstriction, pulmonary arterial smooth muscle cell (PASMC) proliferation, and extracellular matrix synthesis. Selexipag is an IP receptor agonist. The active metabolite of selexipag, ACT-333679, behaved as a full agonist in multiple PAH-relevant receptor-distal-or downstream-cellular assays with a maximal efficacy (Emax) comparable to that of the prototypic PGI2 analog iloprost. In PASMC, ACT-333679 potently induced cellular relaxation (EC50 4.3 nM) and inhibited cell proliferation (IC50 4.0 nM) as well as extracellular matrix synthesis (IC50 8.3 nM). In contrast, ACT-333679 displayed partial agonism in receptor-proximal-or upstream-cAMP accumulation assays (Emax 56%) when compared with iloprost and the PGI2 analogs beraprost and treprostinil (Emax ∼100%). Partial agonism of ACT-333679 also resulted in limited β-arrestin recruitment (Emax 40%) and lack of sustained IP receptor internalization, whereas all tested PGI2 analogs behaved as full agonists in these desensitization-related assays. Reference: J Pharmacol Exp Ther. 2017 Jul;362(1):186-199. https://jpet.aspetjournals.org/content/362/1/186.long
In vivo activity: Selexipag is a novel prostacyclin receptor (IP receptor) agonist approved for the treatment of pulmonary arterial hypertension (PAH). Selexipag is converted to MRE-269 in vivo, and the plasma concentration of MRE-269 is maintained at a therapeutic level for a long time. MRE-269 has selective IP receptor agonist activity and exerts vasodilatory and anti-proliferative effects on pulmonary arterial smooth muscle cells. In a Sugen 5416/hypoxia rat model of PAH, selexipag significantly improved pulmonary artery obstruction, decreased right ventricular systolic pressure, decreased right ventricular hypertrophy and improved survival rate. Reference: Nihon Yakurigaku Zasshi. 2021;156(3):178-186. https://www.jstage.jst.go.jp/article/fpj/156/3/156_20092/_article/-char/ja/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 57.2 115.12
Ethanol 34.5 69.47
DMF 30.0 60.41
PBS (pH 7.2) 1.0 2.01

Preparing Stock Solutions

The following data is based on the product molecular weight 496.62 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Gatfield J, Menyhart K, Wanner D, Gnerre C, Monnier L, Morrison K, Hess P, Iglarz M, Clozel M, Nayler O. Selexipag Active Metabolite ACT-333679 Displays Strong Anticontractile and Antiremodeling Effects but Low β-Arrestin Recruitment and Desensitization Potential. J Pharmacol Exp Ther. 2017 Jul;362(1):186-199. doi: 10.1124/jpet.116.239665. Epub 2017 May 5. PMID: 28476928. 2. Kuwano K, Kosugi K, Fuchikami C, Funaki S. [Pharmacological characteristics and clinical study results of Selexipag (Uptravi® tablets), a selective prostacyclin receptor agonist]. Nihon Yakurigaku Zasshi. 2021;156(3):178-186. Japanese. doi: 10.1254/fpj.20092. PMID: 33952848.
In vitro protocol: 1. Gatfield J, Menyhart K, Wanner D, Gnerre C, Monnier L, Morrison K, Hess P, Iglarz M, Clozel M, Nayler O. Selexipag Active Metabolite ACT-333679 Displays Strong Anticontractile and Antiremodeling Effects but Low β-Arrestin Recruitment and Desensitization Potential. J Pharmacol Exp Ther. 2017 Jul;362(1):186-199. doi: 10.1124/jpet.116.239665. Epub 2017 May 5. PMID: 28476928.
In vivo protocol: 1. Kuwano K, Kosugi K, Fuchikami C, Funaki S. [Pharmacological characteristics and clinical study results of Selexipag (Uptravi® tablets), a selective prostacyclin receptor agonist]. Nihon Yakurigaku Zasshi. 2021;156(3):178-186. Japanese. doi: 10.1254/fpj.20092. PMID: 33952848.

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1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548742/ PubMed PMID: 31644051.

2: Pharmacoeconomic Review Report: Selexipag (Uptravi) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Sep. Available from http://www.ncbi.nlm.nih.gov/books/NBK533876/ PubMed PMID: 30462450.

3: Patient Group Input Submissions: selexipag (Uptravi) for Pulmonary Arterial Hypertension (WHO class II and III) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Sep. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK533882/ PubMed PMID: 30462448.

4: CADTH Canadian Drug Expert Committee Final Recommendation Selexipag: (Uptravi — Actelion Pharmaceuticals Canada Inc.): Indication: Pulmonary Arterial Hypertension [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Oct 26. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK533883/ PubMed PMID: 30462441.

5: Sorensen LM, Wehland M, Kruger M, Simonsen U, Nassef MZ, Infanger M, Grimm D. A Special Focus on Selexipag - Treatment of Pulmonary Arterial Hypertension. Curr Pharm Des. 2017;23(34):5191-5199. doi: 10.2174/1381612823666170908114227. Review. PubMed PMID: 28891448.

6: Noel ZR, Kido K, Macaulay TE. Selexipag for the treatment of pulmonary arterial hypertension. Am J Health Syst Pharm. 2017 Aug 1;74(15):1135-1141. doi: 10.2146/ajhp160798. Epub 2017 May 22. Review. PubMed PMID: 28533253.

7: Honorato Pérez J. Selexipag, a selective prostacyclin receptor agonist in pulmonary arterial hypertension: a pharmacology review. Expert Rev Clin Pharmacol. 2017 Jul;10(7):753-762. doi: 10.1080/17512433.2017.1322900. Epub 2017 May 19. Review. PubMed PMID: 28524738.

8: Bruderer S, Hurst N, Remenova T, Dingemanse J. Clinical pharmacology, efficacy, and safety of selexipag for the treatment of pulmonary arterial hypertension. Expert Opin Drug Saf. 2017 Jun;16(6):743-751. doi: 10.1080/14740338.2017.1328052. Epub 2017 May 23. Review. PubMed PMID: 28494686.

9: Baker WL, Darsaklis K, Singhvi A, Salerno EL. Selexipag, an Oral Prostacyclin-Receptor Agonist for Pulmonary Arterial Hypertension. Ann Pharmacother. 2017 Jun;51(6):488-495. doi: 10.1177/1060028017697424. Epub 2017 Feb 1. Review. PubMed PMID: 28478717.

10: Duggan ST, Keam SJ, Burness CB. Selexipag: A Review in Pulmonary Arterial Hypertension. Am J Cardiovasc Drugs. 2017 Feb;17(1):73-80. doi: 10.1007/s40256-016-0209-9. Review. PubMed PMID: 27988834.

11: Hardin EA, Chin KM. Selexipag in the treatment of pulmonary arterial hypertension: design, development, and therapy. Drug Des Devel Ther. 2016 Nov 15;10:3747-3754. eCollection 2016. Review. PubMed PMID: 27895464; PubMed Central PMCID: PMC5117890.

12: Sardana M, Moll M, Farber HW. Pharmacokinetic drug evaluation of selexipag for the treatment of pulmonary arterial hypertension. Expert Opin Drug Metab Toxicol. 2016 Dec;12(12):1513-1520. Epub 2016 Nov 4. Review. PubMed PMID: 27756196.

13: Ghosh RK, Ball S, Das A, Bandyopadhyay D, Mondal S, Saha D, Gupta A. Selexipag in Pulmonary Arterial Hypertension: Most Updated Evidence From Recent Preclinical and Clinical Studies. J Clin Pharmacol. 2017 May;57(5):547-557. doi: 10.1002/jcph.834. Epub 2016 Dec 21. Review. PubMed PMID: 27670133.

14: Richter MJ, Gall H, Grimminger J, Grimminger F, Ghofrani HA. Selexipag for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2016 Sep;17(13):1825-34. doi: 10.1080/14656566.2016.1215429. Epub 2016 Aug 2. Review. PubMed PMID: 27467883.

15: Scott LJ. Selexipag: First Global Approval. Drugs. 2016 Mar;76(3):413-8. doi: 10.1007/s40265-016-0549-4. Review. PubMed PMID: 26846322.

16: Skoro-Sajer N, Lang IM. Selexipag for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2014 Feb;15(3):429-36. doi: 10.1517/14656566.2014.876007. Epub 2014 Jan 7. Review. PubMed PMID: 24392948.