compound 7 [PMID: 31381331]   Click here for help

GtoPdb Ligand ID: 10450

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 7 selectively inhibits αVβ6 integrin-mediated cell adhesion [1]. It was discovered in a medicinal chemistry effort to rationally design improved therapeutics for idiopathic pulmonary fibrosis (IPF).
Docking studies indicate that compound 7 binds in a pocket formed at the interface of the α and β integrin subunits. Since compound 7 is selective for β6-containing αV integrins we have recorded the binding data against the various β subunits tested, to make comparisons clearer.
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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 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 1
Rotatable bonds 9
Topological polar surface area 82.35
Molecular weight 501.31
XLogP 3.25
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 [O-]C(=O)CC(c1cccc(c1)n1nc(cc1C)C)C[N+]1(C)CCC(C1)CCc1ccc2c(n1)NCCC2
Isomeric SMILES [O-]C(=O)C[C@@H](c1cccc(c1)n1nc(cc1C)C)C[N@@+]1(C)CC[C@H](C1)CCc1ccc2c(n1)NCCC2
InChI InChI=1S/C30H39N5O2/c1-21-16-22(2)34(33-21)28-8-4-6-25(17-28)26(18-29(36)37)20-35(3)15-13-23(19-35)9-11-27-12-10-24-7-5-14-31-30(24)32-27/h4,6,8,10,12,16-17,23,26H,5,7,9,11,13-15,18-20H2,1-3H3,(H-,31,32,36,37)/t23-,26-,35+/m1/s1
InChI Key BXOSGYRJKCYDLH-YAYCEGLDSA-N
Bioactivity Comments
Compound 7 exhibits favourable physicochemical, pharmacodynamic and pharmacokinetic profiles, and does not inhibit hERG channel activity in vitro [1]. It inhibits αVβ6 integrin-mediated cell adhesion with an IC50 of 3.2 nM. Inhibition of cell adhesion for αV integrins with other β subunits is lower (higher IC50 values).
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
integrin, beta 6 subunit Primary target of this compound Hs Inhibitor Inhibition 10.0 pKi - 1
⤷ pKi 10.0 (Ki 1.07x10-10 M) [1]
Description: Determined in a radioligand binding assay.
integrin, beta 1 subunit (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) Hs Inhibitor Inhibition 7.7 pKi - 1
⤷ pKi 7.7 (Ki 2x10-8 M) [1]
Description: Ki estimated from the binding affinity of the test compound to αvβ6 integrin in a radioligand binding assay.
integrin, beta 8 subunit Hs Inhibitor Inhibition 7.6 pKi - 1
⤷ pKi 7.6 (Ki 2.51x10-8 M) [1]
Description: Ki estimated from the binding affinity of the test compound to αvβ6 integrin in a radioligand binding assay.
integrin, beta 5 subunit Hs Inhibitor Inhibition 7.3 pKi - 1
⤷ pKi 7.3 (Ki 5.01x10-8 M) [1]
Description: Ki estimated from the binding affinity of the test compound to αvβ6 integrin in a radioligand binding assay.
integrin, beta 3 subunit (platelet glycoprotein IIIa, antigen CD61) Hs Inhibitor Inhibition 6.8 pKi - 1
⤷ pKi 6.8 (Ki 1.58x10-7 M) [1]
Description: Ki estimated from the binding affinity of the test compound to αvβ6 integrin in a radioligand binding assay.