PF-01247324 - Sodium Channel 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPF-01247324Cat. No.: HY-101383CAS No.: 875051-72-2分式: CHClNO分量: 330.6作靶点: Sodium Channel作通路: Membrane Transporter/Ion Channel储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 30 mg/mL (90.74

2、mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 3.0248 mL 15.1240 mL 30.2480 mL5 mM 0.6050 mL 3.0248 mL 6.0496 mL10 mM 0.3025 mL 1.5124 mL 3.0248 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体

3、内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.56 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.56 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1

4、/2 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (7.56 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 PF-01247324选择性且有服活性的Nav1.8通道阻断物，对类重 组Nav1.8 的IC50值为196 nM。IC50 & Target IC50: 196 nM (hNav1.8) 1体外研究 PF-01247324 inhibits native tetrodotoxin-resistant (TTX-R) currents in human dors

5、al root ganglion (DRG)neurons (IC50=331 nM) and in recombinantly expressed h Nav1.8 channels (IC50=196 nM), with 50-foldselectivity over recombinantly expressed TTX-R hNav1.5 channels (IC50=10 M) and 65-100-fold selectivityover TTX-sensitive (TTX-S) channels (IC50=10-18 M). In vitro current clamp sh

6、ows that PF-01247324reduces excitability in both rat and human DRG neurons and also alters the waveform of the action potential1.体内研究 Experiments n rodents demonstrates efficacy in both inflammatory and neuropathic pain models. PF-01247324 reduces phase 2 flinching by 37% at 100 mg/kg. There is a si

7、gnificant effect of 30 mg/kg of PF-01247324 in the rat model carrageenan-induced thermal hyperalgesia and in CFA-induced mechanicalhyperalgesia at exposures of 0.218 and 0.126 M respectively 1. Mice that received PF-01247324 showssignificant improvements in motor coordination and cerebellar-like sym

8、ptoms compared to control 2.PROTOCOLAnimal Rats: For male Sprague Dawley rats (170-300g), PF-01247324 is formulated as solutions of 0, 10, 30, 100Administration 12 mg/kg in 0.5%MC/0.1%Tween 80 vehicle and dosed via oral gavage prior to behavioural testing. Testanimals are placed in a box separated b

9、y walls with a wire mesh floor allowing access to the plantar surfaceof the paw. Tactile testing is conducted 1.Mice: PF-01247324 is suspended in 0.5% methylcellulose, 0.1% Tween 80 and administered by oral gavageat a dose of 1000 mg/kg in a volume of 10 mL/kg one hour before behavioral testing. Con

10、trol groups areadministered an equal volume of vehicle 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Payne CE, et al. A novel selective and orally bioavailable Nav 1.8 channel blocker, PF-01247324, attenuates nociception and sensoryneuron excitability. Br J Pharmacol. 2015 May;172(10):2654-70.2. Shields SD, et al. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mousemodel of multiple sclerosis. PLoS One. 2015 Mar 6;10(3):e0119067.McePdfHeightCaution: Product has not be