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| Targets |
PF-04856264 targets the voltage-gated sodium channel Nav1.7, which is preferentially expressed in peripheral somatic and visceral sensory neurons, olfactory sensory neurons, and sympathetic ganglion neurons. The compound inhibits the Nav channel by interacting with the S1-S4 voltage sensor segment of homologous domain 4, which is unlike other known NaV inhibitors. This inhibition modulates intracellular Ca²⁺ signaling and chondrocyte secretome.
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| ln Vitro |
PF-04856264 is a potent and selective Nav1.7 inhibitor with IC50s of 28 nM (human), 131 nM (mouse), 19 nM (cynomolgus monkey), and 42 nM (dog). It has low potency against the rat Nav1.7 channel. Inhibition of Nav1.7 modulates intracellular Ca²⁺ signaling and chondrocyte secretome, raising mechanical pain thresholds and inhibiting ERK expression.
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| ln Vivo |
Pain behavior produced by OD1 is reversed by PF-04856264 (3-30 mg/kg; i.p.) [2].
In vivo, PF-04856264 (3-30 mg/kg; i.p.) reverses OD1-induced pain behaviors, demonstrating analgesic and anti-inflammatory effects. The compound raises mechanical pain thresholds and inhibits ERK expression in vivo. These effects support its potential for treating neuropathic pain and other chronic pain disorders. |
| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for PF-04856264 involve voltage-gated sodium channel inhibition assays. IC50 values are determined using patch-clamp electrophysiology on cells expressing recombinant Nav1.7 channels from human, mouse, cynomolgus monkey, and dog. The compound's interaction with the S1-S4 voltage sensor segment is characterized through mutagenesis studies.
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| Cell Assay |
In vitro cell-based assays for PF-04856264 use cell lines expressing recombinant Nav1.7 channels. Patch-clamp electrophysiology is employed to measure inhibition of sodium currents, with IC50 values determined from concentration-response curves. The compound's effects on Ca²⁺ signaling and ERK expression are assessed in chondrocyte cell models.
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| Animal Protocol |
Animal/Disease Models: 6-8 weeks old male C57BL/6J mice (OD1-induced spontaneous pain model) [2]
Doses: 3, 30 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results:Dramatically diminished spontaneous pain in mice pain behavior. In vivo animal studies for PF-04856264 have been conducted in rodent pain models. The compound (3-30 mg/kg; i.p.) reverses OD1-induced pain behaviors. Additional studies evaluate its effects on mechanical pain thresholds and ERK expression in pain models. These studies demonstrate the compound's analgesic and anti-inflammatory efficacy in vivo. |
| ADME/Pharmacokinetics |
PF-04856264 has a molecular formula of C20H15N5O3S2 and a molecular weight of 437.49 g/mol. The IUPAC name is 3-cyano-4-(2-(1-methyl-1H-pyrazol-5-yl)phenoxy)-N-(thiazol-2-yl)benzenesulfonamide. The compound is soluble in DMSO and appears as a solid powder. Purity is ≥98% (HPLC). Storage: dry, dark, at 0-4°C for short term or -20°C for long term.
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| Toxicity/Toxicokinetics |
Specific toxicological data for PF-04856264 are not detailed in the available literature. The compound is classified for research use only and is not intended for human therapeutic applications. As a Nav1.7 inhibitor, potential toxicities would relate to effects on sensory and autonomic neuronal function, though formal toxicological profiles are not reported.
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| References |
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| Additional Infomation |
PF-04856264 (CAS 1235397-05-3) is a potent and selective Nav1.7 inhibitor with IC50s of 28 nM (human), 131 nM (mouse), 19 nM (monkey), and 42 nM (dog). It shows analgesic and anti-inflammatory effects and is used in pain research. The compound inhibits Nav1.7 by interacting with the S1-S4 voltage sensor of domain 4. No clinical trial data are available.
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| Molecular Formula |
C20H15N5O3S2
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| Molecular Weight |
437.492
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| Exact Mass |
437.062
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| CAS # |
1235397-05-3
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| PubChem CID |
71718072
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.162
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
737
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MKSKJVIBSRUWSZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H15N5O3S2/c1-25-17(8-9-23-25)16-4-2-3-5-19(16)28-18-7-6-15(12-14(18)13-21)30(26,27)24-20-22-10-11-29-20/h2-12H,1H3,(H,22,24)
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| Chemical Name |
3-cyano-4-[2-(2-methylpyrazol-3-yl)phenoxy]-N-(1,3-thiazol-2-yl)benzenesulfonamide
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| Synonyms |
PF 04856264; PF04856264; PF-04856264
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~571.44 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2858 mL | 11.4288 mL | 22.8577 mL | |
| 5 mM | 0.4572 mL | 2.2858 mL | 4.5715 mL | |
| 10 mM | 0.2286 mL | 1.1429 mL | 2.2858 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.
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