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compound T.14   Click here for help

GtoPdb Ligand ID: 10385

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: T.14 is a dual action compound that acts as an inhibitor of VEGFR2 (KDR) and the PD-L1 protein [1]. Functionally it has antiangiogenic and immunomodulator actions, that are indicative of experimental anti-tumour potential.
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 7
Topological polar surface area 50.36
Molecular weight 378.11
XLogP 5.65
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 COc1ccc(cc1)C=Cc1cccc(c1)NC(=O)Nc1ccc(cc1)Cl
Isomeric SMILES COc1ccc(cc1)/C=C/c1cccc(c1)NC(=O)Nc1ccc(cc1)Cl
InChI InChI=1S/C22H19ClN2O2/c1-27-21-13-7-16(8-14-21)5-6-17-3-2-4-20(15-17)25-22(26)24-19-11-9-18(23)10-12-19/h2-15H,1H3,(H2,24,25,26)/b6-5+
InChI Key VGWVPSZVSVONQT-AATRIKPKSA-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
T.14 inhibits VEGFR2 kinase activity and resulting tube formation of endothelial cells, plus it enhances the effect of BMS-8 (PubChem CID 117941742) which is a small molecule protein-protein interaction inhibitor that targets the immune inhibitory interaction between PD-1 and its ligand PD-L1 [1-2]. T.14 inhibits VEGFR2 phosphorylation in A549 cells by 82% (sorafenib in the same assay inhibits by 84%), and inhibits HMEC-1 (endothelial) cell tube formation at 100 nM (sorafenib in the same assay requires 10 μM to achieve the same effect). It reduces free PD-L1 by 75%, compared to BMS-8 which reduces free PD-L1 by 32%.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
kinase insert domain receptor Hs Inhibitor Inhibition - - - 1
⤷ [1]
Selectivity at ligand targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
programmed cell death 1 ligand 1 Hs Inhibitor Binding - - - 1
⤷ [1]