compound 13c [PMID: 20684591]   Click here for help

GtoPdb Ligand ID: 9681

Compound class: Synthetic organic
Comment: Compound 13c [PMID: 20684591] is a potent, orally active and competitive inhibitor of all three isoforms of protein kinase D [2]. It is one of the chemical structures claimed in Novartis' patent WO2008122615 [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

compound 13c [PMID: 20684591] is commercially available from our sponsors

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 6
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 65.97
Molecular weight 388.24
XLogP 4.22
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 C1CCC(CC1)Nc1nccc(c1)c1cc2cnccc2c(n1)N1CCNCC1
Isomeric SMILES C1CCC(CC1)Nc1nccc(c1)c1cc2cnccc2c(n1)N1CCNCC1
InChI InChI=1S/C23H28N6/c1-2-4-19(5-3-1)27-22-15-17(6-9-26-22)21-14-18-16-25-8-7-20(18)23(28-21)29-12-10-24-11-13-29/h6-9,14-16,19,24H,1-5,10-13H2,(H,26,27)
InChI Key DIZACSOTRSXCHC-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 13c inhibits all three isoforms of protein kinase D with similar potency [2]. In an HDAC nuclear export assay (a cellular readout of PKD activity), compound 13c inhibited PGF2α-induced nuclear export of GFP-HDAC5 in cardiac myocytes with an IC50 of 32nM. In vivo, 13c reduced cardiac hypertrophy in two rat models. Off target kinase inhibition (inhibited by >50% at 1 μM 13c) was detected for GSK3β, CaMKIIβ, CaMKIIγ, CaMKIIδ and MARK1.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
protein kinase D1 Hs Inhibitor Inhibition 9.2 pIC50 - 2
⤷ pIC50 9.2 (IC50 6x10-10 M) [2]
Description: Measuring inhibition of synthetic substrate phosphorylation in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay.