| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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Purity: ≥98%
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.
| Targets |
human IP receptor ( Ki = 20 nM )
Prostacyclin receptor (IP receptor) agonist[1] |
|---|---|
| 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].
MRE-269 increased cAMP formation in human pulmonary artery smooth muscle cells (hPASMC) in a concentration-dependent manner, and this effect was significantly suppressed by IP receptor antagonists (CAY10441 and another antagonist).[1] MRE-269 induced endothelium-independent vasodilation in rat extralobar pulmonary artery (EPA) precontracted with PGF2α, with maximal relaxation of 96.7% (with endothelium) and 96.3% (without endothelium) of the response to papaverine.[1] In rat small intralobar pulmonary artery (SIPA), MRE-269 also induced strong vasodilation (maximal relaxation 93.5%), which was comparable to its effect in EPA, unlike other IP receptor agonists which showed reduced efficacy in SIPA.[1] The vasodilation induced by MRE-269 was not enhanced by the EP3 receptor antagonist CM9, indicating that its action is not limited by EP3-mediated vasoconstriction.[1] In porcine pulmonary arteries, MRE-269 induced concentration-dependent vasodilation with maximal relaxation of 101.7% relative to papaverine.[1] In human pulmonary arteries, MRE-269 induced concentration-dependent vasodilation that was not significantly different between endothelium-intact and endothelium-denuded preparations, with maximal relaxation of 96% in endothelium-denuded arteries.[1] |
| 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].
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| Enzyme Assay |
cAMP formation assay in human pulmonary artery smooth muscle cells: Cells were seeded in 96-well plates and preincubated in HBSS for 1 hour. Test drugs and the phosphodiesterase inhibitor IBMX were added, and cells were incubated for 5 minutes. cAMP content was determined using a cAMP enzyme immunoassay kit.[1]
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| Cell Assay |
Human pulmonary artery smooth muscle cells (hPASMC) were cultured in smooth muscle cell growth medium. Cells were treated with MRE-269 and other IP receptor agonists, and cAMP levels were measured to assess IP receptor activation.[1]
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| Animal Protocol |
The study used rat pulmonary arteries (EPA and SIPA) isolated from rat left lungs. Arterial rings were mounted in a wire myograph chamber containing Krebs-Ringer bicarbonate solution gassed with 95% O2 and 5% CO2 at 37°C. Rings were precontracted with PGF2α, and cumulative concentrations of test drugs were added to measure relaxation. Endothelium-denuded preparations were used to assess endothelium-independent effects.[1]
Porcine pulmonary arteries were obtained from pig lungs, and human pulmonary arteries were obtained from transplant networks or surgical resections. Similar wire myograph setups were used to measure vasodilation in these tissues.[1] |
| References |
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| Additional Infomation |
ACT-333679 belongs to the pyrazine class of compounds with the chemical formula {4-[(propyl-2-yl)(pyrazin-2-yl)amino]butoxy}acetic acid, with two phenyl substituents attached to the 5 and 6 positions of the pyrazine ring, respectively. It is the active metabolite of the orphan drug selexipag, used to treat pulmonary arterial hypertension (PAH). ACT-333679 has multiple functions, including orphan drug, platelet aggregation inhibitor, prostacyclin receptor agonist, vasodilator, and drug metabolite. It is an aromatic amine, ether, pyrazine compound, sulfonamide, tertiary amine compound, and monocarboxylic acid. MRE-269 is the active metabolite of selexipag (NS-304), a novel non-prostaglandin prostacyclin receptor (IP receptor) agonist used to treat pulmonary arterial hypertension (PAH). [1]
Unlike other IP receptor agonists (eprostol, iloprost, treprostyl, belaprost), MRE-269 is a selective IP receptor agonist that produces endothelium-independent vasodilation and has shown consistent efficacy in arteries of different sizes (EPA and SIPA) and in different species (rats, pigs, and humans). [1] Its vasodilatory effect is not diminished by endothelial removal or inhibition of nitric oxide synthase, suggesting that it may still be effective even under the pathological conditions of endothelial dysfunction in patients with pulmonary hypertension. [1] |
| Molecular Formula |
C25H29N3O3
|
|---|---|
| Molecular Weight |
419.5161
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| Exact Mass |
419.22
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| Elemental Analysis |
C, 71.57; H, 6.97; N, 10.02; O, 11.44
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| CAS # |
475085-57-5
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| Related CAS # |
MRE-269-d7; 1265295-20-2; MRE-269-d6; 1265295-56-4
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| PubChem CID |
9931891
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
602.1±55.0 °C at 760 mmHg
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| Flash Point |
318.0±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.588
|
| LogP |
5.09
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
31
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| Complexity |
518
|
| Defined Atom Stereocenter Count |
0
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| 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
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| 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)
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| Chemical Name |
2-[4-[(5,6-diphenylpyrazin-2-yl)-propan-2-ylamino]butoxy]acetic acid
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| Synonyms |
ACT 333679; MRE 269; MRE-269; ACT333679; ACT-333679; MRE269
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 50~84 mg/mL (119.2~200.2 mM)
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|---|---|
| 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. View More
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. |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02206204 | Completed | Drug: selexipag Drug: moxifloxacin |
Safety Cardiodynamics Pharmacokinetics Tolerability |
Actelion | June 2012 | Phase 1 |
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