PF-01247324 is a novel selective and orally bioavailable Nav 1.8 channel blocker with an IC50 of 196 nM for recombinant human Nav1.8 channel. PF-01247324 inhibits native tetrodotoxin-resistant (TTX-R) currents in human dorsal root ganglion (DRG) neurons (IC50=331 nM) and in recombinantly expressed h Nav1.8 channels (IC50=196 nM), with 50-fold selectivity over recombinantly expressed TTX-R hNav1.5 channels (IC50=10 μM) and 65-100-fold selectivity over TTX-sensitive (TTX-S) channels (IC50=10-18 μM).
In vivo, PF-01247324 (30 mg/kg) showed significant effect in the rat model carrageenan-induced thermal hyperalgesia and in CFA-induced mechanical hyperalgesia at exposures of 0.218 and 0.126 μM respectively.
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| Preparation method | |
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| Incubation time | |
| Animal Experiment | |
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| Animal models | Mice |
| Formulation | suspended in 0.5% methylcellulose, 0.1% Tween 80 |
| Dosages | 1000 mg/kg in a volume of 10 mL/kg |
| Administration | oral gavage |
| Molecular Weight | 330.6 |
| Formula | C13H10Cl3N3O |
| CAS Number | 875051-72-2 |
| Solubility (25°C) | DMSO: ≥ 25 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| 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.
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