kinase inhibitor 2 [PMID: 30199702]   Click here for help

GtoPdb Ligand ID: 10081

Compound class: Synthetic organic
Comment: This compound is reported by Compain et al. (2018) as the protein kinase inhibitor component of a β-glucuronidase-responsive albumin-binding prodrug that was designed as a novel cancer therapeutic [1]. The biological activity of inhibitor 2 is blocked when it is incoprorated in the enzyme-responsive prodrug. The active inhibitor is released only in the presence of β-glucuronidase (e.g. as exists in the tumour microenvironment), so should faciliate selective delivery of the drug to the tumour whilst minimising systemic off-target and adverse effects. Compound 2 is a multi-kinase inhibitor with a similar selectivity profile as seliciclib, but with additional potent inhibitory activity at DYRK3 and GSK3.
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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 7
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 106.05
Molecular weight 456.27
XLogP 4.61
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 NC1CCC(CC1)Nc1nc(NCc2ccc(cc2)c2ccccn2)n2c(n1)c(cn2)C(C)C
Isomeric SMILES N[C@@H]1CC[C@H](CC1)Nc1nc(NCc2ccc(cc2)c2ccccn2)n2c(n1)c(cn2)C(C)C
InChI InChI=1S/C26H32N8/c1-17(2)22-16-30-34-24(22)32-25(31-21-12-10-20(27)11-13-21)33-26(34)29-15-18-6-8-19(9-7-18)23-5-3-4-14-28-23/h3-9,14,16-17,20-21H,10-13,15,27H2,1-2H3,(H2,29,31,32,33)/t20-,21-
InChI Key PRJNNPMIUGYOST-MEMLXQNLSA-N
Bioactivity Comments
Inhibitor 2 exhibits low nanomolar antiproliferative activity against a range of cancer cell lines in vitro [1]. When incorporated in to the prodrug structure the inhibitor is inactive in vitro in the absence of β-glucuronidase (IC50 > 200 nM vs. A549 human lung carcinoma cells), but is fully active when β-glucuronidase is added to the culture medium (IC50 10.3 nM).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
cyclin dependent kinase 9 Hs Inhibitor Inhibition 7.3 pIC50 - 1
⤷ pIC50 7.3 (IC50 4.9x10-8 M) [1]
Description: CDK9/cyclin T
cyclin dependent kinase 5 Hs Inhibitor Inhibition 7.3 pIC50 - 1
⤷ pIC50 7.3 (IC50 5x10-8 M) [1]
Description: CDK5/p25
cyclin dependent kinase 2 Hs Inhibitor Inhibition 7.2 pIC50 - 1
⤷ pIC50 7.2 (IC50 6.8x10-8 M) [1]
Description: CDK2/cyclin A
cyclin dependent kinase 1 Hs Inhibitor Inhibition 7.2 pIC50 - 1
⤷ pIC50 7.2 (IC50 7x10-8 M) [1]
Description: CDK1/cyclin B
CDC like kinase 4 Hs Inhibitor Inhibition 7.1 pIC50 - 1
⤷ pIC50 7.1 (IC50 8.9x10-8 M) [1]
dual specificity tyrosine phosphorylation regulated kinase 3 Hs Inhibitor Inhibition 6.4 pIC50 - 1
⤷ pIC50 6.4 (IC50 3.8x10-7 M) [1]