Synonym
PF-01247324; PF 01247324; PF01247324.
IUPAC/Chemical Name
6-amino-N-methyl-5-(2,3,5-trichlorophenyl)pyridine-2-carboxamide
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)
SMILES Code
O=C(C1=NC(N)=C(C2=CC(Cl)=CC(Cl)=C2Cl)C=C1)NC
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
PF-01247324 is a selective and orally bioavailable Nav1.8 channel blocker with an IC50 of 196 nM for recombinant human Nav1.8 channel.
In vitro activity:
The inhibition of Nav 1.8 channels by PF-01247324 was studied using in vitro patch-clamp electrophysiology and the oral bioavailability and antinociceptive effects demonstrated using in vivo rodent models of inflammatory and neuropathic pain. PF-01247324 inhibited native tetrodotoxin-resistant (TTX-R) currents in human dorsal root ganglion (DRG) neurons (IC50 : 331 nM) and in recombinantly expressed h Nav 1.8 channels (IC50 : 196 nM), with 50-fold selectivity over recombinantly expressed TTX-R hNav 1.5 channels (IC50 : ∼10 μM) and 65-100-fold selectivity over TTX-sensitive (TTX-S) channels (IC50 : ∼10-18 μM). Native TTX-R currents in small-diameter rodent DRG neurons were inhibited with an IC50 448 nM, and the block of both human recombinant Nav 1.8 channels and TTX-R from rat DRG neurons was both frequency and state dependent. In vitro current clamp showed that PF-01247324 reduced excitability in both rat and human DRG neurons and also altered the waveform of the action potential.
Reference: Br J Pharmacol. 2015 May;172(10):2654-70. https://pubmed.ncbi.nlm.nih.gov/25625641/
In vivo activity:
The present study assessed the effect of per os (p.o.) dosing of a new orally bioavailable Nav1.8-selective blocker, PF-01247324, in transgenic mice expressing Nav1.8 in Purkinje neurons, and in wildtype mice in the experimental autoimmune encephalomyelitis (EAE) model. 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. This study observed significant improvements in motor coordination and cerebellar-like symptoms in mice that received PF-01247324 compared to control littermates that received vehicle.
Reference: PLoS One. 2015 Mar 6;10(3):e0119067. https://pubmed.ncbi.nlm.nih.gov/25747279/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
30.0 |
90.75 |
|
| Ethanol |
30.0 |
90.75 |
|
| Ethanol:PBS (pH 7.2) (1:4) |
0.2 |
0.60 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
330.59
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Payne CE, Brown AR, Theile JW, Loucif AJ, Alexandrou AJ, Fuller MD, Mahoney JH, Antonio BM, Gerlach AC, Printzenhoff DM, Prime RL, Stockbridge G, Kirkup AJ, Bannon AW, England S, Chapman ML, Bagal S, Roeloffs R, Anand U, Anand P, Bungay PJ, Kemp M, Butt RP, Stevens EB. A novel selective and orally bioavailable Nav 1.8 channel blocker, PF-01247324, attenuates nociception and sensory neuron excitability. Br J Pharmacol. 2015 May;172(10):2654-70. doi: 10.1111/bph.13092. Epub 2015 Apr 10. PMID: 25625641; PMCID: PMC4409913.
2. Shields SD, Butt RP, Dib-Hajj SD, Waxman SG. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis. PLoS One. 2015 Mar 6;10(3):e0119067. doi: 10.1371/journal.pone.0119067. PMID: 25747279; PMCID: PMC4352054.
In vitro protocol:
1. Payne CE, Brown AR, Theile JW, Loucif AJ, Alexandrou AJ, Fuller MD, Mahoney JH, Antonio BM, Gerlach AC, Printzenhoff DM, Prime RL, Stockbridge G, Kirkup AJ, Bannon AW, England S, Chapman ML, Bagal S, Roeloffs R, Anand U, Anand P, Bungay PJ, Kemp M, Butt RP, Stevens EB. A novel selective and orally bioavailable Nav 1.8 channel blocker, PF-01247324, attenuates nociception and sensory neuron excitability. Br J Pharmacol. 2015 May;172(10):2654-70. doi: 10.1111/bph.13092. Epub 2015 Apr 10. PMID: 25625641; PMCID: PMC4409913.
In vivo protocol:
1. Shields SD, Butt RP, Dib-Hajj SD, Waxman SG. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis. PLoS One. 2015 Mar 6;10(3):e0119067. doi: 10.1371/journal.pone.0119067. PMID: 25747279; PMCID: PMC4352054.
1: Shields SD, Butt RP, Dib-Hajj SD, Waxman SG. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis. PLoS One. 2015 Mar 6;10(3):e0119067. doi: 10.1371/journal.pone.0119067. eCollection 2015. PubMed PMID: 25747279; PubMed Central PMCID: PMC4352054.
2: Payne CE, Brown AR, Theile JW, Loucif AJ, Alexandrou AJ, Fuller MD, Mahoney JH, Antonio BM, Gerlach AC, Printzenhoff DM, Prime RL, Stockbridge G, Kirkup AJ, Bannon AW, England S, Chapman ML, Bagal S, Roeloffs R, Anand U, Anand P, Bungay PJ, Kemp M, Butt RP, Stevens EB. A novel selective and orally bioavailable Nav 1.8 channel blocker, PF-01247324, attenuates nociception and sensory neuron excitability. Br J Pharmacol. 2015 May;172(10):2654-70. doi: 10.1111/bph.13092. Epub 2015 Apr 10. PubMed PMID: 25625641; PubMed Central PMCID: PMC4409913.
