compound 38 [PMID: 24915291]   Click here for help

GtoPdb Ligand ID: 8145

Compound class: Synthetic organic
Comment: Compound 38 is an analogue assessed in a study to design covalent irreversible inhibitors of Bruton's tyrosine kinase (Btk) [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 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 11
Hydrogen bond donors 5
Rotatable bonds 15
Topological polar surface area 154.21
Molecular weight 617.2
XLogP 3.69
No. Lipinski's rules broken 2
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 C=CC(=O)NCC(=O)Nc1cccc(c1)Nc1ncc(cn1)NC(=O)c1cc(ccc1C)NC(=O)c1cccc(c1)C(F)(F)F
Isomeric SMILES C=CC(=O)NCC(=O)Nc1cccc(c1)Nc1ncc(cn1)NC(=O)c1cc(ccc1C)NC(=O)c1cccc(c1)C(F)(F)F
InChI InChI=1S/C31H26F3N7O4/c1-3-26(42)35-17-27(43)38-21-8-5-9-22(13-21)41-30-36-15-24(16-37-30)40-29(45)25-14-23(11-10-18(25)2)39-28(44)19-6-4-7-20(12-19)31(32,33)34/h3-16H,1,17H2,2H3,(H,35,42)(H,38,43)(H,39,44)(H,40,45)(H,36,37,41)
InChI Key SMOPKEHQPPXRSH-UHFFFAOYSA-N
Bioactivity Comments
Compound 38 is highly potent against other Tec family kinases, and the receptor tyrosine kinases, EGFR, HER2 and HER4 [1], most likely by forming a covalent bond with a cysteine residue conserved amongst these proteins.
We have mapped Btk as this compound's primary target based on it being the intended target of the medicinal chemistry design [1], but include other equally well (and more potently) inhibited kinases in the interaction tables below.
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 9.1 pIC50 - 1
⤷ pIC50 9.1 (IC50 7.1x10-10 M) [1]
TXK tyrosine kinase Hs Inhibitor Inhibition 8.9 pIC50 - 1
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [1]
BLK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 8.4 pIC50 - 1
⤷ pIC50 8.4 (IC50 4.2x10-9 M) [1]
Bruton tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition >8.4 pIC50 - 1
⤷ pIC50 >8.4 (IC50 <4.4x10-9 M) [1]
tec protein tyrosine kinase Hs Inhibitor Inhibition 8.2 pIC50 - 1
⤷ pIC50 8.2 (IC50 6.3x10-9 M) [1]
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
erb-b2 receptor tyrosine kinase 4 Hs Inhibitor Inhibition 8.5 pIC50 - 1
⤷ pIC50 8.5 (IC50 3.3x10-9 M) [1]
epidermal growth factor receptor Hs Inhibitor Inhibition 8.1 pIC50 - 1
⤷ pIC50 8.1 (IC50 7x10-9 M) [1]
erb-b2 receptor tyrosine kinase 2 Hs Inhibitor Inhibition 8.1 pIC50 - 1
⤷ pIC50 8.1 (IC50 7x10-9 M) [1]