| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
PF-01247324 is a novel, potent, selective and orally bioavailable Nav1.8 channel blocker with an IC50 of 196 nM for recombinant human Nav1.8 channel. PF-01247324 was administered by oral gavage at 1000 mg/kg; control groups received an equal volume of vehicle. Behavioral assays of motor coordination, grip strength, and ataxia were performed. We observed significant improvements in motor coordination and cerebellar-like symptoms in mice that received PF-01247324 compared to control littermates that received vehicle. These preclinical proof-of-concept data suggest that PF-01247324, its derivatives, or other Nav1.8-selective blockers merit further study for providing symptomatic therapy for cerebellar dysfunction in MS and related disorders. NaV 1.8 ion channels have been highlighted as important molecular targets for the design of low MW blockers for the treatment of chronic pain.
| ln Vitro |
In human dorsal root ganglion (DRG) neurons, PF-01247324 inhibits both native tetrodotoxin-resistant (TTX-R) currents (IC50=331 nM) and recombinantly expressed hNav1.8 channels (IC50=196 nM). The selectivity of PF-01247324 is 50 times higher than that of the recombinantly expressed TTX-R hNav1.5 channel (IC50=10 μM), and 65–100 times higher than that of the TTX-sensitive (TTX-S) channel (IC50=10–18 μM). PF-01247324 was shown to alter the action potential waveform and decrease excitability in both rat and human DRG neurons by in vitro current clamp [1].
|
|---|---|
| ln Vivo |
Its effectiveness in neuropathic pain and inflammatory models was shown in rodent trials. At 100 mg/kg, PF-01247324 decreased phase 2 withdrawal by 37%. PF-01247324, at a dose of 30 mg/kg, significantly mitigates the effects of carrageenan-induced heat hyperalgesia and CFA-induced mechanical hyperalgesia in rat models [1]. When PF-01247324 was administered to mice instead of controls, there were notable improvements in motor coordination and cerebellar-like symptoms [2].
|
| References |
|
| Molecular Formula |
C13H10N3OCL3
|
|---|---|
| Molecular Weight |
330.597
|
| Exact Mass |
328.989
|
| CAS # |
875051-72-2
|
| PubChem CID |
11659955
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
3.971
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
20
|
| Complexity |
358
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
HPIUHDCRVYDAEJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C13H10Cl3N3O/c1-18-13(20)10-3-2-7(12(17)19-10)8-4-6(14)5-9(15)11(8)16/h2-5H,1H3,(H2,17,19)(H,18,20)
|
| Chemical Name |
6-amino-N-methyl-5-(2,3,5-trichlorophenyl)pyridine-2-carboxamide
|
| Synonyms |
PF-01247324; PF 01247324; PF01247324.
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ≥ 30 mg/mL (~90.74 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0248 mL | 15.1240 mL | 30.2480 mL | |
| 5 mM | 0.6050 mL | 3.0248 mL | 6.0496 mL | |
| 10 mM | 0.3025 mL | 1.5124 mL | 3.0248 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 PF-01247324 is a selective Nav1.8 channel subtype-selective inhibitor.
Antiallodynic effects of PF-01247324 in neuropathic pain. PF-01247324 reduced tactile allodynia in a spinal nerve ligation model (L5) of nerve injury.Br J Pharmacol. 2015 May; 172(10): 2654–2670. |
|---|
 Inhibition by PF-01247324 is both use and state dependent at hNav1.8 channels and TTX-R in rat DRG neurons. Block of recombinant hNav1.8 and native TTX-R channels by PF-01247324 was assessed using voltage protocols designed to vary the amount of steady-state inactivation. |
 Potency and selectivity for Nav1.8 channels can be achieved at the LA binding site.Br J Pharmacol. 2015 May; 172(10): 2654–2670. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
