GAT100   Click here for help

GtoPdb Ligand ID: 9237

Synonyms: 5-(cyanosulfanyl)-3-ethyl-N-{2-[4-(piperidin-1-yl)phenyl]ethyl}-1H-indole-2-carboxamide
Compound class: Synthetic organic
Comment: GAT100 is a potent negative allosteric modulator (NAM) of the cannabinoid CB1 receptor, which exhibits irreversible binding [2-3]. GAT100 can be utilised as a covalent probe for mapping structure-function characteristics, which define the druggable CB1 receptor allosteric binding site. GAT100 is one of the compounds claimed in patent WO2015027160 [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
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 4
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 97.22
Molecular weight 432.2
XLogP 5.28
No. Lipinski's rules broken 1

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 N#CSc1ccc2c(c1)c(CC)c([nH]2)C(=O)NCCc1ccc(cc1)N1CCCCC1
Isomeric SMILES N#CSc1ccc2c(c1)c(CC)c([nH]2)C(=O)NCCc1ccc(cc1)N1CCCCC1
InChI InChI=1S/C25H28N4OS/c1-2-21-22-16-20(31-17-26)10-11-23(22)28-24(21)25(30)27-13-12-18-6-8-19(9-7-18)29-14-4-3-5-15-29/h6-11,16,28H,2-5,12-15H2,1H3,(H,27,30)
InChI Key OZEQTGDZTPJNAR-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
GAT100 is a NAM of the orthosteric CB1 receptor agonist CP55940 and the endocannabinoids 2-arachidonoylglycerol and anandamide as assessed by several measures of receptor activation and intracellular signalling. GAT100 was found to display functional selectivity, being a more potent NAM of β-arrestin1 recruitment than for inhibition of ERK1/2 and cAMP assays [2-3]. GAT100 shows no evidence of inverse agonist activity, which it is hoped will mitigate the undesirable psychological and somatic side-effects associated with existing CB1 receptor inverse agonist compounds.
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
CB1 receptor Hs Allosteric modulator Negative 6.4 – 7.7 pEC50 - 2-3
⤷ pEC50 7.7 (EC50 1.92x10-8 M) [2]
Description: Although GAT100 antagonized CP55940-induced stimulation of [35S]GTPγS binding to human CB1 CHO cell membranes, it enhanced the binding of [3H]CP55940 to these membranes. The EC50 and Emax values of GAT100 for this enhancement, with the 95% confidence limits shown in brackets, were 19.6 nM (10.4 & 36.9 nM) and 116.5% (108.3 & 124.6%), respectively. GAT100 (500 nM) was also found to enhance saturation binding of [3H]CP55940 to human CB1 HEK293 cell membranes.
pEC50 6.4 (EC50 4.098x10-7 M) [3]
Description: Measuring GAT100's inhibition of [3H]SR141716A binding, in radioligand binding assays