GNE-616   Click here for help

GtoPdb Ligand ID: 10355

Synonyms: compound 24 [PMID: 30943032] | GNE616
Compound class: Synthetic organic
Comment: GNE-616 is an arylsulfonamide class voltage gated sodium channel inhibitor that is selective for the Nav1.7 isoform [5]. This class of inhibitors are channel blockers that bind to the fourth voltage sensing domain (VSD4) of the channel and lock it into the inactivated state [1,6]. Nav1.7 is a mechanistic target that is being pursued for the treatment of chronic pain [2-4,6-7].
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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 7
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 105.69
Molecular weight 537.15
XLogP 4.04
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 Fc1cc2c(cc1S(=O)(=O)Nc1ccncn1)OCCC2N1CCC(CC1c1ccccn1)C(F)(F)F
Isomeric SMILES Fc1cc2c(cc1S(=O)(=O)Nc1ccncn1)OCC[C@@H]2N1CC[C@@H](C[C@@H]1c1ccccn1)C(F)(F)F
InChI InChI=1S/C24H23F4N5O3S/c25-17-12-16-19(33-9-5-15(24(26,27)28)11-20(33)18-3-1-2-7-30-18)6-10-36-21(16)13-22(17)37(34,35)32-23-4-8-29-14-31-23/h1-4,7-8,12-15,19-20H,5-6,9-11H2,(H,29,31,32)/t15-,19-,20+/m0/s1
InChI Key XQUOWYVEKSXNET-RYGJVYDSSA-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, Chapman ML, Marron BE, Prime R, Storer RI, Swain NA. (2014)
Recent progress in sodium channel modulators for pain.
Bioorg Med Chem Lett, 24 (16): 3690-9. [PMID:25060923]
2. Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y et al.. (2006)
An SCN9A channelopathy causes congenital inability to experience pain.
Nature, 444 (7121): 894-8. [PMID:17167479]
3. Gingras J, Smith S, Matson DJ, Johnson D, Nye K, Couture L, Feric E, Yin R, Moyer BD, Peterson ML et al.. (2014)
Global Nav1.7 knockout mice recapitulate the phenotype of human congenital indifference to pain.
PLoS ONE, 9 (9): e105895. [PMID:25188265]
4. Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C, Hossain S, Pape T, Payne B, Radomski C, Donaldson G, Ives E, Cox J, Younghusband HB, Green R, Duff A, Boltshauser E, Grinspan GA, Dimon JH, Sibley BG, Andria G, Toscano E, Kerdraon J, Bowsher D, Pimstone SN, Samuels ME, Sherrington R, Hayden MR. (2007)
Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations.
Clin Genet, 71 (4): 311-9. [PMID:17470132]
5. McKerrall SJ, Nguyen T, Lai KW, Bergeron P, Deng L, DiPasquale A, Chang JH, Chen J, Chernov-Rogan T, Hackos DH et al.. (2019)
Structure- and Ligand-Based Discovery of Chromane Arylsulfonamide Nav1.7 Inhibitors for the Treatment of Chronic Pain.
J Med Chem, 62 (8): 4091-4109. [PMID:30943032]
6. McKerrall SJ, Sutherlin DP. (2018)
Nav1.7 inhibitors for the treatment of chronic pain.
Bioorg Med Chem Lett, 28 (19): 3141-3149. [PMID:30139550]
7. Shields SD, Deng L, Reese RM, Dourado M, Tao J, Foreman O, Chang JH, Hackos DH. (2018)
Insensitivity to Pain upon Adult-Onset Deletion of Nav1.7 or Its Blockade with Selective Inhibitors.
J Neurosci, 38 (47): 10180-10201. [PMID:30301756]