A-803467   Click here for help

GtoPdb Ligand ID: 5734

Synonyms: A 803467 | A803467
PDB Ligand
Compound class: Synthetic organic
Comment: A-803467 is a voltage-gated sodium (Nav) channel inhibitor, with selectivity for the Nav subtype. It has been used in experimantal work to investigate the link between Nav1.8 knockdown and inflammatory and neuropathic pain. Since A-803467 exhibits poor oral pharmacokinetics in preclinical models, an optimised compound was designed in the form of PF-04885614, which is orally bioavailable and has improved selectivty and a reduced (but still not ideal) hERG liability [1].
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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

A-803467 is commercially available from our sponsors

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 2
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 60.7
Molecular weight 357.08
XLogP 4.1
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 COc1cc(cc(c1)OC)NC(=O)c1ccc(o1)c1ccc(cc1)Cl
Isomeric SMILES COc1cc(cc(c1)OC)NC(=O)c1ccc(o1)c1ccc(cc1)Cl
InChI InChI=1S/C19H16ClNO4/c1-23-15-9-14(10-16(11-15)24-2)21-19(22)18-8-7-17(25-18)12-3-5-13(20)6-4-12/h3-11H,1-2H3,(H,21,22)
InChI Key VHKBTPQDHDSBSP-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/)
References
1. Bagal SK, Kemp MI, Bungay PJ, Hay TL, Murata Y, Payne CE, Stevens EB, Brown A, Blakemore DC, Corbett MS et al.. (2016)
Discovery and optimisation of potent and highly subtype selective Nav1.8 inhibitors with reduced cardiovascular liabilities.
Med. Chem. Commun, 7: 1925-1931. DOI: 10.1039/C6MD00281A
2. Jarvis MF, Honore P, Shieh CC, Chapman M, Joshi S, Zhang XF, Kort M, Carroll W, Marron B, Atkinson R et al.. (2007)
A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat.
Proc Natl Acad Sci USA, 104 (20): 8520-5. [PMID:17483457]