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MGS0274

Cat. No. M21266
MGS0274  Structure
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Biological Activity

MGS0274 is a lipid-soluble precursor drug for the mGlu2 and mGlu3 receptor agonist MGS0008, which improves oral bioavailability. mGS0274 has potential for use in the study of schizophrenia.

Chemical Information
Molecular Weight 429.48
Formula C21H32FNO7
CAS Number 1501974-69-1
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] Motoki Ochi, et al. Xenobiotica. Bottom-up physiologically based pharmacokinetic modelling for predicting the human pharmacokinetic profiles of the ester prodrug MGS0274 and its active metabolite MGS0008, a metabotropic glutamate 2/3 receptor agonist

[2] Hiroki Urabe, et al. Eur J Med Chem. Discovery of MGS0274, an ester prodrug of a metabotropic glutamate receptor 2/3 agonist with improved oral bioavailability

[3] Mai Watanabe, et al. Br J Clin Pharmacol. Safety and pharmacokinetic profiles of MGS0274 besylate (TS-134), a novel metabotropic glutamate 2/3 receptor agonist prodrug, in healthy subjects

[4] Kohnosuke Kinoshita, et al. Pharmacol Res Perspect. Preclinical disposition of MGS0274 besylate, a prodrug of a potent group II metabotropic glutamate receptor agonist MGS0008 for the treatment of schizophrenia

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