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MRE-269(ACT-333679)

Cat. No. M21029
MRE-269(ACT-333679) Structure
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Biological Activity

MRE-269(ACT-333679) is a prostaglandin I2 (IP) receptor agonist with a binding affinity for the human IP receptor that is 130-fold greater than that for other human prostanoid receptor.

Chemical Information
Molecular Weight 419.52
Formula C25H29N3O3
CAS Number 475085-57-5
Solubility (25°C) DMSO 84 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Shun-Bin Luo, et al. Pharm Biol. Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles

[2] Katarina Zmajkovicova, et al. Am J Respir Cell Mol Biol. The Antifibrotic Activity of Prostacyclin Receptor Agonism Is Mediated through Inhibition of YAP/TAZ

[3] John Gatfield, et al. J Pharmacol Exp Ther. Selexipag Active Metabolite ACT-333679 Displays Strong Anticontractile and Antiremodeling Effects but Low β-Arrestin Recruitment and Desensitization Potential

[4] N N Orie, et al. Prostaglandins Other Lipid Mediat. Differential actions of the prostacyclin analogues treprostinil and iloprost and the selexipag metabolite, MRE-269 (ACT-333679) in rat small pulmonary arteries and veins

[5] Keith Morrison, et al. J Pharmacol Exp Ther. Differential effects of Selexipag [corrected] and prostacyclin analogs in rat pulmonary artery

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