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Purity: ≥98%
ICA-121431 is a potent, highly selective small molecule inhibitor of the human Nav1.3 and Nav1.1 voltage gated sodium channels with IC50 of 19 nM. It exhibit up to 1,000-fold selectivity for human Nav1.3/Nav1.1 (ICA-121431, IC50, 19 nM) vs. other TTX-sensitive or resistant (i.e., Nav1.5) sodium channels, in other words, it has little or no activity against human Nav1.5 or Nav1.7 channels. Voltage-gated sodium channels initiate action potentials in brain neurons, and sodium channel blockers are used in therapy of epilepsy.
| ln Vitro |
Human Nav1.3 and the amino acid residues that might determine this channel's selectivity over other related Nav channels, such as Nav1.7 and Nav1.5, are interacting with ICA-121431. Data produced with a pulse protocol that involves an 8-s step to a voltage that inactivates half of the channels before a 20-ms test pulse using traditional patch clamp electrophysiological recording[1]. ICA-121431 exhibits IC50s of 0.013 µM, >30 µM, and 12 µM for Wild type hNav1.3, hNav1.5, and hNav1.7, respectively[1]. hNav1.3 M1 (S1510Y), hNav1.3 M2 (R1511W), hNav1.3 M3 (E1559D), hNav1.3 M1, 3 (S1510Y/E1559D), hNav1.3 M2, 3 (R1511W/E1559D), hNav1.3 M1, 2, 3 (S1510Y/R1511W/E1559D), and hNav1.7 M1, 2, 3 (Y1537S/W1538R/D1586E) have IC50 values of 0.1 µM, 0.37 µM, 1.1 µM, 1.3 µM, 11.6 µM, and 0.032 µM, respectively[1]. hNav1.3/hNav1.5 S1-S4, hNav1.3/hNav1.5 S3-S4, hNav1.3/hNav1.5 S5-S6, hNav1.3/hNav1.7 S1, hNav1.3/hNav1.7 S2, and hNav1.3/hNav1 are among the hNav channels that ICA-121431 is against. The IC50 values of hNav1.3/hNav1.7 S5-S6, 7 S3-S4, 1.2 µM, 11 µM, 2.0 µM, 0.045 µM, 0.030 µM, 0.30 µM, 1.0 µM, and 0.024 µM, respectively, were reported[1].
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| ln Vivo |
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| Animal Protocol |
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| References |
[1]. McCormack K, et al. Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels.Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):E2724-32.
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| Molecular Formula |
C23H19N3O3S2
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| Molecular Weight |
449.54
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| CAS # |
313254-51-2
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| Related CAS # |
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| SMILES |
O=C(NC1=CC=C(S(NC2=NC=CS2)(=O)=O)C=C1)C(C3=CC=CC=C3)C4=CC=CC=C4
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.56 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 25.0 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: 2.5 mg/mL (5.56 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2245 mL | 11.1225 mL | 22.2450 mL | |
| 5 mM | 0.4449 mL | 2.2245 mL | 4.4490 mL | |
| 10 mM | 0.2224 mL | 1.1122 mL | 2.2245 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.
Properties of Navchannel inhibition by ICA-121431.
Pharmacological and biophysical properties of Nav1.3 and Nav1.7 M123 triple mutant.Proc Natl Acad Sci U S A.2013 Jul 16;110(29):E2724-32. |
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(A) Defining interaction region on Nav1.3 required for inhibition by ICA-121431.Proc Natl Acad Sci U S A.2013 Jul 16;110(29):E2724-32. |
 Defining amino acid residues important for inhibition of Nav1.3 by ICA-121431.
Selective Nav1.7 inhibitor also interacts with Domain 4 voltage sensor.
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COA
Species orthologs of Nav1.7 exhibit different sensitivities to inhibition by ICA-121431 and PF-04856264.