compound 31 [PMID: 24915291]   Click here for help

GtoPdb Ligand ID: 8148

Compound class: Synthetic organic
Comment: Compound 31 is a novel 2,5-diaminopyrimidin based analogue repoted as an irreversible inhibitor of Bruton’s tyrosine kinase (Btk) [1]. The selectivity profile of this compound differs from that of ibrutinib, the first irreversible Btk inhibitor discovered.
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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 9
Hydrogen bond donors 4
Rotatable bonds 12
Topological polar surface area 125.11
Molecular weight 560.18
XLogP 4.52
No. Lipinski's rules broken 0

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 C=CC(=O)Nc1cccc(c1)Nc1ncc(cn1)NC(=O)c1cc(ccc1C)NC(=O)c1cccc(c1)C(F)(F)F
Isomeric SMILES C=CC(=O)Nc1cccc(c1)Nc1ncc(cn1)NC(=O)c1cc(ccc1C)NC(=O)c1cccc(c1)C(F)(F)F
InChI InChI=1S/C29H23F3N6O3/c1-3-25(39)35-20-8-5-9-21(13-20)38-28-33-15-23(16-34-28)37-27(41)24-14-22(11-10-17(24)2)36-26(40)18-6-4-7-19(12-18)29(30,31)32/h3-16H,1H2,2H3,(H,35,39)(H,36,40)(H,37,41)(H,33,34,38)
InChI Key BTWVWABAWDKQNJ-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
Compound 31 exhibits antitumour activity in vivo [1]. Compound 31 is potently active against several B-cell receptor signalling pathway related kinases, including all but one member of the Tec family kinases and the Src family kinase Blk, but is not active against Syk or PKC and is only weakly active at JAK2 [1]. The compound has activity against three screened receptor tyrosine kinases, EGFR, HER2 and HER4 (IC50s are 11, 19 and 5.5nM respectively) [1]. We have tagged Btk as the primary target of this compound as this was the intended target of the medicinal chemistry study, although it is not the most effectively inhibited kinase..
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
BMX non-receptor tyrosine kinase Hs Inhibitor Inhibition 8.7 pIC50 - 1
⤷ pIC50 8.7 (IC50 1.9x10-9 M) [1]
TXK tyrosine kinase Hs Inhibitor Inhibition 8.7 pIC50 - 1
⤷ pIC50 8.7 (IC50 1.9x10-9 M) [1]
BLK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 8.6 pIC50 - 1
⤷ pIC50 8.6 (IC50 2.7x10-9 M) [1]
Bruton tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 8.4 pIC50 - 1
⤷ pIC50 8.4 (IC50 5x10-9 M) [1]
tec protein tyrosine kinase Hs Inhibitor Inhibition 8.1 pIC50 - 1
⤷ pIC50 8.1 (IC50 8.2x10-9 M) [1]