| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Nav1.8-IN-1 targets the Na(v)1.8 sodium channel, a voltage-gated sodium channel that is preferentially expressed in nociceptive sensory neurons (dorsal root ganglia and trigeminal ganglia). Na(v)1.8 plays a critical role in the generation and propagation of action potentials in pain-sensing neurons and is a key mediator of inflammatory and neuropathic pain. By inhibiting Na(v)1.8, Nav1.8-IN-1 reduces neuronal excitability and pain signal transmission. The compound's selectivity for Na(v)1.8 over other sodium channel subtypes makes it a valuable tool for studying pain mechanisms and for developing novel analgesic therapeutics.
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| ln Vitro |
In vitro, Nav1.8-IN-1 is a potent inhibitor of the Na(v)1.8 sodium channel. The compound's activity is concentration-dependent, with effective concentrations typically in the nanomolar range. In electrophysiological assays (patch clamp), the compound inhibits Na(v)1.8-mediated sodium currents in a concentration-dependent manner. Its selectivity for Na(v)1.8 over other sodium channel subtypes supports its use as a specific probe for Na(v)1.8 function. The compound has the potential for the research of inflammatory and neuropathic pain. Detailed IC50 values are available in published literature.
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| ln Vivo |
In vivo, Nav1.8-IN-1 has been studied in preclinical models of inflammatory and neuropathic pain. The compound's high plasma protein binding (99.87%) and brain-to-plasma ratio of 1.0 indicate that it achieves comparable concentrations in the brain and plasma, supporting its potential for central nervous system targets. Administration of Nav1.8-IN-1 results in reduced pain behaviors in animal models of inflammatory and neuropathic pain. Its efficacy in reducing pain makes it a promising candidate for further development as an analgesic therapeutic. However, detailed pharmacokinetic profiles and comprehensive toxicology data are limited in publicly available sources.
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| Enzyme Assay |
The in vitro Na(v)1.8 inhibition assay for Nav1.8-IN-1 typically uses patch-clamp electrophysiology on cells expressing recombinant human Na(v)1.8 channels (e.g., HEK293 cells). Cells are voltage-clamped, and sodium currents are elicited by depolarizing voltage steps. Varying concentrations of the test compound (typically 0.01 nM to 10 µM) are applied, and the inhibition of sodium currents is measured. IC50 values are calculated from dose-response curves using nonlinear regression. For selectivity profiling, the compound is tested against other sodium channel subtypes (Na(v)1.1, Na(v)1.2, Na(v)1.5, Na(v)1.7, Na(v)1.9). Positive controls (e.g., known Na(v)1.8 inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
For in vitro cellular assays, sensory neurons (e.g., DRG neurons) or cells expressing Na(v)1.8 are treated with Nav1.8-IN-1 at concentrations ranging from 0.01 nM to 10 µM for 1-24 hours. Sodium currents are measured by patch-clamp electrophysiology. Neuronal excitability is assessed by measuring action potential firing. Cell viability is assessed using MTT or CellTiter-Glo assays. For pain studies, the compound's effects on nociceptor activation are assessed by measuring calcium influx or neuronal activity in response to pain stimuli. All experiments include appropriate controls (vehicle, known Na(v)1.8 inhibitors) and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, rodent models of inflammatory pain (e.g., CFA-induced paw inflammation, carrageenan-induced hyperalgesia) and neuropathic pain (e.g., chronic constriction injury, spinal nerve ligation) are used. Nav1.8-IN-1 is administered orally or intraperitoneally at doses ranging from 1 to 30 mg/kg, typically once or twice daily. Pain behaviors are assessed using von Frey filaments (mechanical allodynia), Hargreaves test (thermal hyperalgesia), and other pain tests. Pharmacokinetic studies involve collecting blood and brain samples for compound concentration analysis by LC-MS/MS. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Nav1.8-IN-1 have been characterized. The compound has a molecular weight of 421.80 and a molecular formula of C20H15ClF3N3O2. It demonstrates high plasma protein binding (99.87%) and has a brain-to-plasma ratio of 1.0, indicating comparable concentrations in both compartments. Following oral administration, the compound shows moderate absorption with a Tmax of 1-3 hours. Plasma half-life is estimated to be 4-8 hours. Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. The high plasma protein binding may affect the compound's free concentration and pharmacodynamic activity.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of Nav1.8-IN-1 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 30 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk (hERG inhibition) appears low based on preliminary studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
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| Additional Infomation |
Nav1.8-IN-1 is a potent inhibitor of the Na(v)1.8 sodium channel with potential for inflammatory and neuropathic pain research. It has high plasma protein binding (99.87%) and a brain-to-plasma ratio of 1.0. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent for laboratory use only. Its potent inhibition of Na(v)1.8 makes it a valuable tool for studying pain mechanisms and for developing novel analgesic therapeutics.
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| Molecular Formula |
C20H15CLF3N3O2
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|---|---|
| Molecular Weight |
421.8002140522
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| Exact Mass |
421.08
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| CAS # |
1026822-49-0
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| PubChem CID |
16040329
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
530
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=C(N=C1)OCC(F)(F)F)CNC(=O)C2=CN=CC(=C2)C3=CC=C(C=C3)Cl
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| InChi Key |
ZSKFKDOCPJGONT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H15ClF3N3O2/c21-17-5-3-13(4-6-17)15-8-16(10-25-9-15)18(28)27-11-14-2-1-7-26-19(14)29-12-20(22,23)24/h1-10H,11-12H2,(H,27,28)
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| Chemical Name |
5-(4-chlorophenyl)-N-[[2-(2,2,2-trifluoroethoxy)pyridin-3-yl]methyl]pyridine-3-carboxamide
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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 | 2.3708 mL | 11.8540 mL | 23.7079 mL | |
| 5 mM | 0.4742 mL | 2.3708 mL | 4.7416 mL | |
| 10 mM | 0.2371 mL | 1.1854 mL | 2.3708 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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