compound 66 [PMID: 19788238]   Click here for help

GtoPdb Ligand ID: 8141

PDB Ligand
Compound class: Synthetic organic
Comment: Compound 66 is reported as a potent ephrin receptor inhibitor designed as part of a structure-based optimisation study [1]. Compound 66 inhibits all ephrin receptors except EphA7 (1118nM) with low nanomolar IC50s (1-40nM) [1]. Modelling suggests that EphA7 is an outlier as it has a bulky isoleucine residue at its gatekeeper position, compared to a smaller threonine in this position in all of the other ephrin receptors[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 3
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 106.03
Molecular weight 417.14
XLogP 5.2
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 COc1ccccc1n1c(cn2c1nc1c2c(=O)[nH]c(=O)n1C)c1cc(O)ccc1C
Isomeric SMILES COc1ccccc1n1c(cn2c1nc1c2c(=O)[nH]c(=O)n1C)c1cc(O)ccc1C
InChI InChI=1S/C22H19N5O4/c1-12-8-9-13(28)10-14(12)16-11-26-18-19(25(2)22(30)24-20(18)29)23-21(26)27(16)15-6-4-5-7-17(15)31-3/h4-11,28H,1-3H3,(H,24,29,30)
InChI Key JTWMOWRMSZZHDR-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
Non-ephrin receptor kinase off-targtes include Src, Lck, Yes1, CSK, BTK,and HER4 [1]. Note that we have tagged EphB1 as the primary target for this compound only as this receptor has the lowest IC50 value. The interaction table below shows that this compound has a high level of inhibitory activity at most of the other ephrin receptors.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
EPH receptor B1 Primary target of this compound Hs Inhibitor Inhibition 9.0 pIC50 - 1
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [1]
EPH receptor B2 Hs Inhibitor Inhibition 8.9 pIC50 - 1
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [1]
EPH receptor B4 Hs Inhibitor Inhibition 8.8 pIC50 - 1
⤷ pIC50 8.8 (IC50 1.6x10-9 M) [1]
EPH receptor A2 Hs Inhibitor Inhibition 8.6 pIC50 - 1
⤷ pIC50 8.6 (IC50 2.3x10-9 M) [1]
EPH receptor A1 Hs Inhibitor Inhibition 8.5 pIC50 - 1
⤷ pIC50 8.5 (IC50 2.9x10-9 M) [1]
EPH receptor A5 Hs Inhibitor Inhibition 8.5 pIC50 - 1
⤷ pIC50 8.5 (IC50 3x10-9 M) [1]
EPH receptor A4 Hs Inhibitor Inhibition 8.5 pIC50 - 1
⤷ pIC50 8.5 (IC50 3.3x10-9 M) [1]
EPH receptor A8 Hs Inhibitor Inhibition 8.4 pIC50 - 1
⤷ pIC50 8.4 (IC50 4.5x10-9 M) [1]
EPH receptor B3 Hs Inhibitor Inhibition 7.8 pIC50 - 1
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [1]
EPH receptor A3 Hs Inhibitor Inhibition 7.4 pIC50 - 1
⤷ pIC50 7.4 (IC50 4x10-8 M) [1]
EPH receptor A7 Hs Inhibitor Inhibition 5.9 pIC50 - 1
⤷ pIC50 5.9 (IC50 1.118x10-6 M) [1]