| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
IC50: 21 nM (human Nav1.7)[1]
The primary target of PF-05186462 is the voltage-gated sodium channel Nav1.7, which is predominantly expressed in peripheral sensory neurons and plays a critical role in pain signaling. PF-05186462 is a potent and selective inhibitor of Nav1.7 with an IC50 of 21 nM. By inhibiting Nav1.7, PF-05186462 blocks the initiation and propagation of action potentials in pain-sensing neurons, thereby exerting analgesic effects. The compound's high selectivity for Nav1.7 over other sodium channels makes it a valuable tool for pain research. |
|---|---|
| ln Vitro |
In HEK293 cells, PF-05186462 inhibits human Nav1.7 channels (IC50=21 nM)[1]. A high rate of plasma protein binding is demonstrated by PF-05186462[1].
In vitro, PF-05186462 potently inhibits Nav1.7 with an IC50 of 21 nM. The compound shows significant selectivity for Nav1.7 versus other sodium channels (Nav1.1, 1.2, 1.3, 1.4, 1.5, 1.6, and 1.8). This high selectivity is a key feature that contributes to its potential as a non-opioid analgesic. PF-05186462 is a small molecule with a molecular weight of 531.89 g/mol and is available with a purity of 99.69%. |
| ln Vivo |
In vivo, PF-05186462 can be used for the research of acute or chronic pain. By inhibiting Nav1.7 in peripheral sensory neurons, the compound can reduce pain signaling without the addictive potential of opioids. However, detailed in vivo efficacy data in specific pain models are not extensively reported in the available literature. Further studies are needed to fully characterize its in vivo effects and therapeutic potential.
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| Enzyme Assay |
In vitro assays for PF-05186462 typically involve measuring its inhibition of Nav1.7 channel activity using electrophysiological techniques such as patch-clamp recording in cell lines expressing recombinant hNav1.7 channels. The compound is applied to the cells at varying concentrations (typically 0.1-1000 nM), and the resulting inhibition of sodium current is measured. The IC50 of 21 nM is determined by fitting concentration-response curves. Selectivity assays against other sodium channel subtypes (Nav1.1-1.8) are also performed to assess the compound's specificity.
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| Cell Assay |
Cellular assays for PF-05186462 typically use cell lines expressing recombinant Nav1.7 channels, such as HEK293 or CHO cells. The compound is applied to the cells, and its effects on channel activity are assessed using electrophysiological techniques such as patch-clamp recording. Fluorescent-based membrane potential assays using voltage-sensitive dyes can also be used for higher-throughput screening of channel activity. Cells are treated with PF-05186462 at various concentrations (e.g., 1-1000 nM), and the inhibition of sodium current or changes in membrane potential are measured. The IC50 for channel inhibition is determined from the concentration-response data.
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| Animal Protocol |
In vivo animal studies for PF-05186462 would typically involve the administration of the compound to rodent models of pain, such as the formalin test, CFA-induced inflammatory pain model, or neuropathic pain models. The compound could be administered via oral gavage or intraperitoneal injection, and its analgesic effects would be assessed by measuring pain-related behaviors such as paw withdrawal latency, mechanical allodynia, or thermal hyperalgesia. Pharmacokinetic parameters and the compound's ability to penetrate the central nervous system may also be evaluated. However, specific in vivo study protocols for PF-05186462 are not detailed in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for PF-05186462 are not extensively reported in the available literature. The compound has a molecular weight of 531.89 g/mol and a molecular formula of C19H10ClF4N5O3S2. It is available with a purity of 99.69%. For research purposes, the compound is typically stored under recommended conditions as per the Certificate of Analysis. Detailed parameters such as half-life, volume of distribution, and bioavailability are not publicly available and would need to be determined experimentally.
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| Toxicity/Toxicokinetics |
There is no specific toxicity data reported for PF-05186462 in the available literature. As a research chemical intended for laboratory use only, it should be handled with standard safety precautions for handling chemical reagents. The compound is not approved for human therapeutic use. Researchers should consult the material safety data sheet (MSDS) for detailed safety and handling information. Any potential toxicity would need to be assessed through formal toxicological studies if the compound were to be developed further.
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| References |
[1]. Jones HM, et, al. Clinical Micro-Dose Studies to Explore the Human Pharmacokinetics of Four Selective Inhibitors of Human Nav1.7 Voltage-Dependent Sodium Channels. Clin Pharmacokinet. 2016 Jul;55(7):875-887.
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| Additional Infomation |
PF-05186462 is a potent and selective inhibitor of human Nav1.7 with an IC50 of 21 nM. It has a molecular formula of C19H10ClF4N5O3S2 and a molecular weight of 531.89 g/mol. PF-05186462 shows significant selectivity for Nav1.7 versus other sodium channels. It can be used for the research of acute or chronic pain and is available with a purity of 99.69%.
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| Molecular Formula |
C19H10CLF4N5O3S2
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|---|---|
| Molecular Weight |
531.891013622284
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| Exact Mass |
530.984
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| CAS # |
1235406-03-7
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| PubChem CID |
46841787
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| Appearance |
White to off-white solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
793
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=C(C=C1C(F)(F)F)C2=CN=NC=C2)OC3=CC(=C(C=C3Cl)S(=O)(=O)NC4=NN=CS4)F
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| InChi Key |
ZAGGUCLXSCVDCK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H10ClF4N5O3S2/c20-13-6-17(34(30,31)29-18-28-27-9-33-18)14(21)7-16(13)32-15-2-1-11(19(22,23)24)5-12(15)10-3-4-25-26-8-10/h1-9H,(H,28,29)
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| Chemical Name |
5-chloro-2-fluoro-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.8801 mL | 9.4004 mL | 18.8009 mL | |
| 5 mM | 0.3760 mL | 1.8801 mL | 3.7602 mL | |
| 10 mM | 0.1880 mL | 0.9400 mL | 1.8801 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.
Link: https://clinicaltrials.gov/ct2/show/NCT01165736
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