 Chemical Structure.png)
MRE-269 (also known as MRE269; ACT-333679), an active metabolite of selexipag (also known as NS-304), is a novel, potent along-acting and selective IP (prostaglandin I2) receptor agonist. MRE-269 (ACT-333679) possesses a strong binding affinity—130 times higher than that of other human prostanoid receptors—for the human IP receptor.
Physicochemical Properties
| Molecular Formula | C25H29N3O3 |
| Molecular Weight | 419.5161 |
| Exact Mass | 419.22 |
| Elemental Analysis | C, 71.57; H, 6.97; N, 10.02; O, 11.44 |
| CAS # | 475085-57-5 |
| Related CAS # | MRE-269-d7; 1265295-20-2; MRE-269-d6; 1265295-56-4 |
| PubChem CID | 9931891 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 602.1±55.0 °C at 760 mmHg |
| Flash Point | 318.0±31.5 °C |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.588 |
| LogP | 5.09 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 31 |
| Complexity | 518 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O(C([H])([H])C(=O)O[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N(C1=C([H])N=C(C2C([H])=C([H])C([H])=C([H])C=2[H])C(C2C([H])=C([H])C([H])=C([H])C=2[H])=N1)C([H])(C([H])([H])[H])C([H])([H])[H] |
| 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) |
| Chemical Name | 2-[4-[(5,6-diphenylpyrazin-2-yl)-propan-2-ylamino]butoxy]acetic acid |
| Synonyms | ACT 333679; MRE 269; MRE-269; ACT333679; ACT-333679; MRE269 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | human IP receptor ( Ki = 20 nM ) |
| ln Vitro | MRE-269 causes the rat extralobar pulmonary artery (EPA) to vasodilate without the need for endothelium. MRE-269 or other IP receptor agonists including epoprostenol, iloprost, treprostinil and beraprost increase cAMP levels in hPASMC[1]. MRE-269 causes vasodilation in LPA(+), LPA(-), and SPA(-) in response to concentration[3]. |
| ln Vivo | MRE-269 exhibits the same vasorelaxant effects on rat small intralobar pulmonary artery (SIPA) and EPA, whereas other IP receptor agonists cause less vasodilation in SIPA compared to EPA[1]. MRE-269 significantly relaxes the rat small pulmonary artery, but its effects don't become noticeable until high concentrations above 10 μM (pEC50, 4.98±0.22). On the other hand, MRE-269 causes only slight relaxation in rat small pulmonary veins across the whole concentration range, with the two highest doses of MRE-269—10 and 100 μM—producing the only notable relaxation[2]. |
| References |
[1]. 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. [2]. 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. [3]. A long-acting and highly selective prostacyclin receptor agonist prodrug, 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (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. |
| Additional Infomation | ACT-333679 is a member of the class of pyrazines that is {4-[(propan-2-yl)(pyrazin-2-yl)amino]butoxy}acetic acid carrying two additional phenyl substituents at positions 5 and 6 on the pyrazine ring. The active metabolite of selexipag, an orphan drug used for the treatment of pulmonary arterial hypertension. It has a role as an orphan drug, a platelet aggregation inhibitor, a prostacyclin receptor agonist, a vasodilator agent and a drug metabolite. It is an aromatic amine, an ether, a member of pyrazines, a sulfonamide, a tertiary amino compound and a monocarboxylic acid. |
Solubility Data
| Solubility (In Vitro) | DMSO: 50~84 mg/mL (119.2~200.2 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.96 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.96 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3837 mL | 11.9184 mL | 23.8368 mL | |
| 5 mM | 0.4767 mL | 2.3837 mL | 4.7674 mL | |
| 10 mM | 0.2384 mL | 1.1918 mL | 2.3837 mL |