CDK12 inhibitor 2   Click here for help

GtoPdb Ligand ID: 10063

Compound class: Synthetic organic
Comment: This compound is a novel and selective cyclin-dependent kinase 12 (CDK12) and CDK13 inhibitor [1]. It is a chemical probe that is suitable for functional studies of CDK12, and a scaffold for further drug discovery efforts. CDK12 is an oncology drug target as its inhibition sensitises cancer cells to DNA-damaging reagents and DNA-repair inhibitors. The chemical structure was generated from the SMILES string supplied with the original J Med Chem article by Ito et al. (2018) [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 7
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 103.05
Molecular weight 532.26
XLogP 6.16
No. Lipinski's rules broken 1
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 N#Cc1ccc(nc1)NC1CCC(CC1)N(c1ccc(cc1)c1ccc(=O)n(c1)C)C(=O)NCc1ccccc1
Isomeric SMILES N#Cc1ccc(nc1)N[C@@H]1CC[C@H](CC1)N(c1ccc(cc1)c1ccc(=O)n(c1)C)C(=O)NCc1ccccc1
InChI InChI=1S/C32H32N6O2/c1-37-22-26(10-18-31(37)39)25-8-13-28(14-9-25)38(32(40)35-20-23-5-3-2-4-6-23)29-15-11-27(12-16-29)36-30-17-7-24(19-33)21-34-30/h2-10,13-14,17-18,21-22,27,29H,11-12,15-16,20H2,1H3,(H,34,36)(H,35,40)/t27-,29-
InChI Key HDJBGURZVALLMD-KWQFAZJVSA-N
Bioactivity Comments
This kinase inhibitor (2) is selective for CDK12/13 over other related C-terminal domain kinases. In a kinome wide-selectivity screen only TAOK1, DYRK2, and STK39 were inhibited by >80% at 1 μM compound. As these kinases play no functional roles in splicing or RNA processing, their inhibition by this compound is unlikely to impact analysis of its use in the investigation of RNA biology. Functional efficacy of inhibitor 2 was demonstrated in vitro by its ability to reduce phosphorylation of RNA polymerase II at its C-terminal domain Ser2 residue in SK-BR-3 cells and to inhibit cell growth [1].
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 13 Primary target of this compound Hs Inhibitor Inhibition 8.0 pIC50 - 1
⤷ pIC50 8.0 (IC50 1x10-8 M) [1]
cyclin dependent kinase 12 Primary target of this compound Hs Inhibitor Inhibition 7.3 pIC50 - 1
⤷ pIC50 7.3 (IC50 5.2x10-8 M) [1]
cyclin dependent kinase 7 Hs Inhibitor Inhibition <5.0 pIC50 - 1
⤷ pIC50 <5.0 (IC50 >1x10-5 M) [1]
cyclin dependent kinase 8 Hs Inhibitor Inhibition <5.0 pIC50 - 1
⤷ pIC50 <5.0 (IC50 >1x10-5 M) [1]
cyclin dependent kinase 9 Hs Inhibitor Inhibition 4.8 pIC50 - 1
⤷ pIC50 4.8 (IC50 1.6x10-5 M) [1]