retigabine   Click here for help

GtoPdb Ligand ID: 2601

Synonyms: AWD-21360 | D-23129 | ezogabine | Potiga® | Trobalt® | WAY-143841
Approved drug PDB Ligand
retigabine is an approved drug (FDA and EMA (2011))
Compound class: Synthetic organic
Comment: Retigabine is unique among antiepileptic drugs in that it functions by activating selected voltage-gated potassium channels in the brain (i.e. Kv7 family channels) [4] [5].
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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

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View more information in the IUPHAR Pharmacology Education Project: retigabine

retigabine 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 CDK toolkit. 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 5
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 76.38
Molecular weight 303.14
XLogP 2.57
No. Lipinski's rules broken 0
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.

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Canonical SMILES CCOC(=O)Nc1ccc(cc1N)NCc1ccc(cc1)F
Isomeric SMILES CCOC(=O)Nc1ccc(cc1N)NCc1ccc(cc1)F
InChI InChI=1S/C16H18FN3O2/c1-2-22-16(21)20-15-8-7-13(9-14(15)18)19-10-11-3-5-12(17)6-4-11/h3-9,19H,2,10,18H2,1H3,(H,20,21)
InChI Key PCOBBVZJEWWZFR-UHFFFAOYSA-N
References
1. Dupuis DS, Schrøder RL, Jespersen T, Christensen JK, Christophersen P, Jensen BS, Olesen SP. (2002)
Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352.
Eur J Pharmacol, 437 (3): 129-37. [PMID:11890900]
2. Li X, Zhang Q, Guo P, Fu J, Mei L, Lv D, Wang J, Lai D, Ye S, Yang H et al.. (2021)
Molecular basis for ligand activation of the human KCNQ2 channel.
Cell Res, 31 (1): 52-61. [PMID:32884139]
3. Liu R, Tzounopoulos T, Wipf P. (2019)
Synthesis and Optimization of Kv7 (KCNQ) Potassium Channel Agonists: The Role of Fluorines in Potency and Selectivity.
ACS Med Chem Lett, 10 (6): 929-935. DOI: 10.1021/acsmedchemlett.9b00097 [PMID:31223450]
4. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA. (2000)
Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine.
Mol Pharmacol, 58 (2): 253-62. [PMID:10908292]
5. Rogawski MA, Bazil CW. (2008)
New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels.
Curr Neurol Neurosci Rep, 8 (4): 345-52. [PMID:18590620]
6. Tatulian L, Delmas P, Abogadie FC, Brown DA. (2001)
Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine.
J Neurosci, 21 (15): 5535-45. [PMID:11466425]
7. Wainger BJ, Macklin EA, Vucic S, McIlduff CE, Paganoni S, Maragakis NJ, Bedlack R, Goyal NA, Rutkove SB, Lange DJ et al.. (2021)
Effect of Ezogabine on Cortical and Spinal Motor Neuron Excitability in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.
JAMA Neurol, 78 (2): 186-196. [PMID:33226425]