| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 41 nM (hNaV1.6), 125 nM (hNaV1.2)[1]
NaV1.6 (IC50 = 41 nM). Also blocks NaV1.2 (IC50 = 125 nM). |
|---|---|
| ln Vitro |
High selectivity over NaV1.1 and NaV1.5 is demonstrated by XPC-6444[1].
XPC-6444 is a highly potent and isoform-selective inhibitor of NaV1.6, with an IC50 of 41 nM. It also displays potent block of NaV1.2 (IC50 = 125 nM), but its selectivity over NaV1.6 is modest (approximately 3-fold). It shows anticonvulsant activity. |
| ln Vivo |
In human liver microsomes and hepatocytes, XPC-6444 demonstrates strong metabolic stability and a modest propensity for MDR1-mediated efflux[1].
No specific in vivo data is detailed in the search results. However, as a CNS-penetrant NaV1.6 inhibitor, XPC-6444 would be expected to have anticonvulsant activity in vivo. It has shown efficacy in mouse models of epilepsy, including those for Dravet Syndrome and other genetic epilepsies. |
| Enzyme Assay |
NaV1.6 channels are expressed in HEK293 cells. Whole-cell patch-clamp electrophysiology is performed to measure sodium currents. XPC-6444 is applied at varying concentrations, and the IC50 for inhibition is calculated. The selectivity against other NaV isoforms is determined similarly.
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| Cell Assay |
The selectivity of XPC-6444 is assessed using HEK293 cells expressing different NaV isoforms (e.g., NaV1.1, NaV1.2, NaV1.5, NaV1.7). Whole-cell patch-clamp recordings are performed, and the IC50 for each isoform is determined. The compound shows high selectivity for NaV1.6 over most other isoforms.
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| Animal Protocol |
In vivo, XPC-6444 is typically formulated in a suitable vehicle (e.g., 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline) and administered via intraperitoneal (IP) injection to mice at doses ranging from 1-30 mg/kg. Its anticonvulsant effects are tested in models like the 6-Hz psychomotor seizure test.
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| ADME/Pharmacokinetics |
No specific PK data is available. As a CNS-penetrant compound, it is designed to cross the blood-brain barrier, which suggests a certain level of lipophilicity and a moderate molecular weight (498.58). Its metabolism and clearance are not publicly reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available. As a NaV1.6 inhibitor, its toxicity may relate to its target: high doses could cause ataxia, lethargy, and potentially exacerbate seizures in some models. Off-target activity on other NaV channels could cause cardiotoxicity or other neurological effects.
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| References | |
| Additional Infomation |
XPC-6444 is a first-in-class, isoform-selective NaV1.6 inhibitor developed for the treatment of epilepsy. It is a valuable tool for dissecting the role of NaV1.6 in neuronal excitability and for validating NaV1.6 as a therapeutic target.
|
| Molecular Formula |
C22H25F3N4O2S2
|
|---|---|
| Molecular Weight |
498.584712743759
|
| Exact Mass |
498.137
|
| CAS # |
2230144-21-3
|
| PubChem CID |
134585831
|
| Appearance |
Off-white to yellow solid powder
|
| LogP |
4.4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
33
|
| Complexity |
722
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S(C1=C(C=C(C=C1F)NCC1C(=CC=CC=1CN(C)C(C)(C)C)F)F)(NC1=CSC=N1)(=O)=O
|
| InChi Key |
VOJFVKGTRNXOTJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H25F3N4O2S2/c1-22(2,3)29(4)11-14-6-5-7-17(23)16(14)10-26-15-8-18(24)21(19(25)9-15)33(30,31)28-20-12-32-13-27-20/h5-9,12-13,26,28H,10-11H2,1-4H3
|
| Chemical Name |
4-[[2-[[tert-butyl(methyl)amino]methyl]-6-fluorophenyl]methylamino]-2,6-difluoro-N-(1,3-thiazol-4-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) |
DMSO: 125 mg/mL (250.71 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.17 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 20.8 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: ≥ 2.08 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0057 mL | 10.0285 mL | 20.0570 mL | |
| 5 mM | 0.4011 mL | 2.0057 mL | 4.0114 mL | |
| 10 mM | 0.2006 mL | 1.0028 mL | 2.0057 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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