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DS-1971a

Cat. No. M21271
DS-1971a  Structure
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Biological Activity

DS-1971a is a potent, homozygous form-selective aryl sulfonamide NaV1.7 inhibitor for the treatment of neuropathic pain.

Chemical Information
Molecular Weight 465.93
Formula C20H21ClFN5O3S
CAS Number 1450595-86-4
Solubility (25°C) DMSO ≥ 60 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] Daigo Asano, et al. Drug Metab Dispos. Physiologically Based Pharmacokinetic Modeling for Quantitative Prediction of Exposure to a Human Disproportionate Metabolite of the Selective NaV1.7 Inhibitor DS-1971a, a Mixed Substrate of Cytochrome P450 and Aldehyde Oxidase, Using Chimeric Mice With Humanized Liver

[2] Daigo Asano, et al. Drug Metab Dispos. CYP2C8-Mediated Formation of a Human Disproportionate Metabolite of the Selective NaV1.7 Inhibitor DS-1971a, a Mixed Cytochrome P450 and Aldehyde Oxidase Substrate

[3] Daigo Asano, et al. Xenobiotica. Evaluation of species differences in the metabolism of the selective NaV1.7 inhibitor DS-1971a, a mixed substrate of cytochrome P450 and aldehyde oxidase

[4] Tsuyoshi Shinozuka, et al. J Med Chem. Discovery of DS-1971a, a Potent, Selective NaV1.7 Inhibitor

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