XPC-5462   Click here for help

GtoPdb Ligand ID: 13387

Synonyms: XPC5462
Compound class: Synthetic organic
Comment: XPC-5462 is one of a set of brain penetrant voltage-gated sodium channel (NaV) inhibitor compounds [1] that were developed to test the hypothesis that NaV1.6 is the principal determinant of the anti-seizure efficacy of NaV inhibitors. NaV1.6 selectivity reduces side-effects that are caused by less selective inhibitors at additional channel isoforms, namely NaV1.1 (in inhibitory interneurons) and NaV1.5 (in cardiomyocytes). XPC-5462 inhibits currents across both NaV1.6 and NaV1.2 channels.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 107.48
Molecular weight 486.51
XLogP 1.28
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES C1CN(C1)CC2=C(CNC3=CC(=C(C(=C3)F)S(=O)(=O)NC4=CSC=N4)F)C(=CC=C2F)F
Isomeric SMILES N1(CCC1)CC2=C(CNC3=CC(=C(C(=C3)F)S(=O)(=O)NC=4N=CSC4)F)C(=CC=C2F)F
InChI InChI=1S/C20H18F4N4O2S2/c21-15-2-3-16(22)14(9-28-4-1-5-28)13(15)8-25-12-6-17(23)20(18(24)7-12)32(29,30)27-19-10-31-11-26-19/h2-3,6-7,10-11,25,27H,1,4-5,8-9H2
InChI Key OTYLSXLIPYTHJE-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
XPC-5462 is equipotent at NaV1.6 and NaV1.2. The IC50 values for the inhibitor set at NaV1.6 compared to the clinically used anti-epileptic medications phenytoin and carbamazepine produces the order XPC-6591 < XPC-5462 < XPC-7198 < XPC-7224 < XPC-4509 < phenytoin < carbamazepine.
Selectivity at ion channels
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Nav1.6 Hs Inhibitor Inhibition 8.0 pIC50 - 1
⤷ pIC50 8.0 (IC50 1.03x10-8 M) [1]
Description: Concentration responses were measured at holding potentials where channels were maintained at fully inactivated potentials.
Nav1.2 Hs Inhibitor Inhibition 8.0 pIC50 - 1
⤷ pIC50 8.0 (IC50 1.09x10-8 M) [1]
Description: Concentration responses were measured at holding potentials where channels were maintained at fully inactivated potentials.
Nav1.6 Mm Inhibitor Inhibition 7.9 pIC50 - 1
⤷ pIC50 7.9 (IC50 1.37x10-8 M) [1]
Description: Concentration responses were measured at holding potentials where channels were maintained at fully inactivated potentials.