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Chemical Structure| 313254-51-2 Chemical Structure| 313254-51-2

Structure of ICA-121431
CAS No.: 313254-51-2

Chemical Structure| 313254-51-2

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ICA-121431 is a nanomolar class potent broad-spectrum voltage-gated sodium channel (Nav) blocker with equivalent selectivity for human Nav1.1 and Nav1.3 subtypes with IC50s less than 20 nM. ICA-121431 had a weak inhibitory effect on human Nav1.2 (IC50=240 nM), and showed greater than 1000-fold selectivity (IC50s >10 µM) for human Nav1.4, Nav1.5, Nav1.6, Nav1.7, and Nav1.8 channels. ICA-121431 can inhibit Nav1.7 channel in rats (IC50=19nM).

Synonyms: ICA-121431

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Product Details of ICA-121431

CAS No. :313254-51-2
Formula : C23H19N3O3S2
M.W : 449.55
SMILES Code : O=C(NC1=CC=C(S(NC2=NC=CS2)(=O)=O)C=C1)C(C3=CC=CC=C3)C4=CC=CC=C4
Synonyms :
ICA-121431
MDL No. :MFCD00992334
InChI Key :URSQNPPONHUJDL-UHFFFAOYSA-N
Pubchem ID :998021

Safety of ICA-121431

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H319-H413
Precautionary Statements:P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
iNeurons 20 nM and 100 nM 5 minutes To validate functional expression of Nav1.3 in iNeurons and assess the blocking effect of ICA-121431 on Na+ currents. Results showed that 20 nM ICA-121431 blocked 11±2% of peak transient inward Na+ current and 24±5% of persistent Na+ current. Brain. 2024 Apr 4;147(4):1247-1263
hippocampal CA1 pyramidal neurons 100 nM 15 minutes ICA-121431 significantly increased the dendritic spike threshold and decreased the rate of rise of dendritic spikes in epileptic animals. Brain. 2023 Jun 1;146(6):2399-2417
rat trigeminal ganglion neurons 1 μM evaluate the reversal effect of ICA-121431 on mechanical hypersensitivity induced by trigeminal nerve injury J Neurosci. 2021 Oct 27;41(43):8991-9007
GH3b6 cells 1 µM ICA-121431 reduced the amplitude of Na+ currents in GH3b6 cells, almost abolishing the current evoked by depolarizing pulse from -50 mV. Int J Mol Sci. 2022 Jan 13;23(2):827

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Vagally-innervated esophageal striated muscle preparation De-sheathed vagus nerve segment 10 µM 30 minutes To evaluate the effect of ICA-121431 on conduction in vagal motor fibers. Results showed that ICA-121431 failed to inhibit contractions or to alter TTX concentration-inhibition curves. Physiol Res. 2020 Dec 31;69(Suppl 3):S471-S478
Mice Kainate model of chronic epilepsy Gavage 0.5 mg/kg body weight Twice daily during the experiment ICA-121431 improves degraded hippocampal spatial representations in epileptic mice and reverses hippocampal memory deficits. Brain. 2023 Jun 1;146(6):2399-2417
Rats Chronic constriction injury model of the trigeminal nerve Local injection 1 μM Single administration Evaluate the reversal effect of ICA-121431 on mechanical hypersensitivity induced by trigeminal nerve injury J Neurosci. 2021 Oct 27;41(43):8991-9007
Mouse Cortical GABAergic neuron culture model In vitro administration 100 nM Single dose To evaluate the inhibitory effect of ICA-121431 on action potential output in GABAergic neurons and observe the rescue effect of peptide 16. Results showed ICA-121431 significantly suppressed neuronal activity, while peptide 16 partially restored action potential firing. ACS Med Chem Lett. 2019 Oct 25;11(3):353-357
Sprague-Dawley rats Infraorbital nerve entrapment model Cumulative application in ex vivo nerve recordings 1 μM 35 minutes ICA-121431 alone did not affect Aδ-fiber signal propagation, but cumulative application with A-803467 and 4,9-anhydro-TTX significantly reduced the Aδ-fiber CAP in IoNE rats. Neurobiol Pain. 2022 Jan 21;11:100084

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.22mL

0.44mL

0.22mL

11.12mL

2.22mL

1.11mL

22.24mL

4.45mL

2.22mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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