MRE-269 | MRE269 | CAS#475085-57-5 | prostacyclin receptor agonist

MRE-269
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 522411

CAS#: 475085-57-5

Description: MRE-269, also known as ACT-333679, is a long-acting and highly selective prostacyclin receptor agonist. MRE-269, the active form or metabolite of Selexipag (NS-304), is much more selective for the IP receptor than are the prostacyclin analogs beraprost and iloprost, which also have high affinity for the EP(3) receptor.

Chemical Structure

MRE-269

CAS# 475085-57-5

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522411
Name: MRE-269
CAS#: 475085-57-5
Chemical Formula: C25H29N3O3
Exact Mass: 419.22
Molecular Weight: 419.525
Elemental Analysis: C, 71.57; H, 6.97; N, 10.02; O, 11.44

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 310
10mg	USD 540
50mg	USD 1700
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: MRE-269; MRE269; MRE 269; ACT-333679; ACT 333679; ACT333679.

IUPAC/Chemical Name: 2-(4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)acetic acid

InChi Key: OJQMKCBWYCWFPU-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H29N3O3/c1-19(2)28(15-9-10-16-31-18-23(29)30)22-17-26-24(20-11-5-3-6-12-20)25(27-22)21-13-7-4-8-14-21/h3-8,11-14,17,19H,9-10,15-16,18H2,1-2H3,(H,29,30)

SMILES Code: CC(N(CCCCOCC(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

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Product Data:

Product Data

Instruction:

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Biological target:	MRE-269 is an active metabolite of selexipag, and acts as a selective IP receptor agonist.
In vitro activity:	Prostacyclin (PGI(2)) and its analogs are useful for the treatment of various vascular disorders, but their half-lives are too short for widespread clinical application. To overcome this drawback, we have synthesized a novel diphenylpyrazine derivative, 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), a prodrug of the active form [4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]acetic acid (MRE-269). NS-304 is an orally available and potent agonist for the PGI(2) receptor (IP receptor). The inhibition constant (K(i)) of MRE-269 for the human IP receptor was 20 nM; in contrast, the K(i) values for other prostanoid receptors were >2.6 microM. MRE-269 was therefore a highly selective agonist for the IP receptor. Reference: J Pharmacol Exp Ther. 2007 Sep;322(3):1181-8. https://pubmed.ncbi.nlm.nih.gov/17545310/
In vivo activity:	MRE-269 induced endothelium-independent vasodilation of rat extralobar pulmonary artery (EPA). The vasorelaxant effects of MRE-269 on rat small intralobar pulmonary artery (SIPA) and EPA were the same, while the other IP receptor agonists induced less vasodilation in SIPA than in EPA. Furthermore, a prostaglandin E receptor 3 antagonist enhanced the vasodilation induced by all IP receptor agonists tested except MRE-269. Reference: Eur J Pharmacol. 2017 Jan 15;795:75-83. https://pubmed.ncbi.nlm.nih.gov/27919660/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	14.0	33.37
	DMSO	48.7	116.00
	Ethanol	15.0	35.75
	Ethanol:PBS (pH 7.2) (1:3)	0.3	0.60

Preparing Stock Solutions

The following data is based on the product molecular weight 419.53 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.

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. Kuwano K, Hashino A, Asaki T, Hamamoto T, Yamada T, Okubo K, Kuwabara K. 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. doi: 10.1124/jpet.107.124248. Epub 2007 Jun 1. PMID: 17545310. 2. Fuchikami C, Murakami K, Tajima K, Homan J, Kosugi K, Kuramoto K, Oka M, Kuwano K. A comparison of vasodilation mode among selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide]), its active metabolite MRE-269 and various prostacyclin receptor agonists in rat, porcine and human pulmonary arteries. Eur J Pharmacol. 2017 Jan 15;795:75-83. doi: 10.1016/j.ejphar.2016.11.057. Epub 2016 Dec 3. PMID: 27919660. 3. Orie NN, Ledwozyw A, Williams DJ, Whittle BJ, Clapp LH. Differential actions of the prostacyclin analogues treprostinil and iloprost and the selexipag metabolite, MRE-269 (ACT-333679) in rat small pulmonary arteries and veins. Prostaglandins Other Lipid Mediat. 2013 Oct;106:1-7. doi: 10.1016/j.prostaglandins.2013.07.003. Epub 2013 Jul 18. PMID: 23872196.
In vitro protocol:	1. Kuwano K, Hashino A, Asaki T, Hamamoto T, Yamada T, Okubo K, Kuwabara K. 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. doi: 10.1124/jpet.107.124248. Epub 2007 Jun 1. PMID: 17545310.
In vivo protocol:	1. Fuchikami C, Murakami K, Tajima K, Homan J, Kosugi K, Kuramoto K, Oka M, Kuwano K. A comparison of vasodilation mode among selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide]), its active metabolite MRE-269 and various prostacyclin receptor agonists in rat, porcine and human pulmonary arteries. Eur J Pharmacol. 2017 Jan 15;795:75-83. doi: 10.1016/j.ejphar.2016.11.057. Epub 2016 Dec 3. PMID: 27919660. 2. Orie NN, Ledwozyw A, Williams DJ, Whittle BJ, Clapp LH. Differential actions of the prostacyclin analogues treprostinil and iloprost and the selexipag metabolite, MRE-269 (ACT-333679) in rat small pulmonary arteries and veins. Prostaglandins Other Lipid Mediat. 2013 Oct;106:1-7. doi: 10.1016/j.prostaglandins.2013.07.003. Epub 2013 Jul 18. PMID: 23872196.

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1: Asaki T, Kuwano K, Morrison K, Gatfield J, Hamamoto T, Clozel M. Selexipag: An Oral and Selective IP Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension. J Med Chem. 2015 Sep 24;58(18):7128-37. doi: 10.1021/acs.jmedchem.5b00698. Epub 2015 Sep 16. PubMed PMID: 26291199.

2: 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.

3: Orie NN, Ledwozyw A, Williams DJ, Whittle BJ, Clapp LH. Differential actions of the prostacyclin analogues treprostinil and iloprost and the selexipag metabolite, MRE-269 (ACT-333679) in rat small pulmonary arteries and veins. Prostaglandins Other Lipid Mediat. 2013 Oct;106:1-7. doi: 10.1016/j.prostaglandins.2013.07.003. Epub 2013 Jul 18. PubMed PMID: 23872196.

4: Benyahia C, Boukais K, Gomez I, Silverstein A, Clapp L, Fabre A, Danel C, Leséche G, Longrois D, Norel X. A comparative study of PGI2 mimetics used clinically on the vasorelaxation of human pulmonary arteries and veins, role of the DP-receptor. Prostaglandins Other Lipid Mediat. 2013 Dec;107:48-55. doi: 10.1016/j.prostaglandins.2013.07.001. Epub 2013 Jul 12. PubMed PMID: 23850788.

5: Kotzki S, Roustit M, Arnaud C, Boutonnat J, Blaise S, Godin-Ribuot D, Cracowski JL. Anodal iontophoresis of a soluble guanylate cyclase stimulator induces a sustained increase in skin blood flow in rats. J Pharmacol Exp Ther. 2013 Sep;346(3):424-31. doi: 10.1124/jpet.113.205484. Epub 2013 Jul 9. PubMed PMID: 23838678.

6: Morrison K, Studer R, Ernst R, Haag F, Kauser K, Clozel M. Differential effects of Selexipag [corrected] and prostacyclin analogs in rat pulmonary artery. J Pharmacol Exp Ther. 2012 Dec;343(3):547-55. doi: 10.1124/jpet.112.197152. Epub 2012 Aug 23. Erratum in: J Pharmacol Exp Ther. 2013 Jan;344(1):317. PubMed PMID: 22918043.

7: Van Ly D, Burgess JK, Brock TG, Lee TH, Black JL, Oliver BG. Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2012 Aug 1;303(3):L239-50. doi: 10.1152/ajplung.00097.2012. Epub 2012 May 25. PubMed PMID: 22637153.

8: Liu B, Luo W, Zhang Y, Li H, Zhu N, Huang D, Zhou Y. Role of cyclooxygenase-1-mediated prostacyclin synthesis in endothelium-dependent vasoconstrictor activity of porcine interlobular renal arteries. Am J Physiol Renal Physiol. 2012 May 1;302(9):F1133-40. doi: 10.1152/ajprenal.00604.2011. Epub 2012 Feb 1. PubMed PMID: 22301626.

9: Morrison K, Ernst R, Hess P, Studer R, Clozel M. Selexipag: a selective prostacyclin receptor agonist that does not affect rat gastric function. J Pharmacol Exp Ther. 2010 Oct;335(1):249-55. doi: 10.1124/jpet.110.169748. Epub 2010 Jul 21. PubMed PMID: 20660124.

10: Kuwano K, Hashino A, Noda K, Kosugi K, Kuwabara K. A long-acting and highly selective prostacyclin receptor agonist prodrug, 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetam ide (NS-304), ameliorates rat pulmonary hypertension with unique relaxant responses of its active form, {4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid (MRE-269), on rat pulmonary artery. J Pharmacol Exp Ther. 2008 Sep;326(3):691-9. doi: 10.1124/jpet.108.138305. Epub 2008 Jun 13. PubMed PMID: 18552131.

11: Kuwano K, Hashino A, Asaki T, Hamamoto T, Yamada T, Okubo K, Kuwabara K. 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetam ide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther. 2007 Sep;322(3):1181-8. Epub 2007 Jun 1. PubMed PMID: 17545310.

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