GSK329   Click here for help

GtoPdb Ligand ID: 11806

Synonyms: compound 47 [PMID: 34699203] | GSK-329
PDB Ligand
Compound class: Synthetic organic
Comment: GSK329 is a small molecule inhibitor of cardiac-specific kinase TNNI3K (TNNI3 interacting kinase) [1]. It was derived from the scaffold of the multi-kinase inhibitor sorafenib (IC50 100nM vs. TNNI3K). GSK329 is suitable as an in vivo tool to assess inhibition of TNNI3K as a novel therapeutic strategy for the treatment of cardiovascular diseases.
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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

GSK329 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 3
Rotatable bonds 8
Topological polar surface area 88.17
Molecular weight 471.05
XLogP 4.94
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 CNc1ncnc(c1)Oc1c(Cl)cc(cc1Cl)NC(=O)Nc1cccc(c1)C(F)(F)F
Isomeric SMILES CNc1cc(Oc2c(Cl)cc(NC(=O)Nc3cccc(c3)C(F)(F)F)cc2Cl)ncn1
InChI InChI=1S/C19H14Cl2F3N5O2/c1-25-15-8-16(27-9-26-15)31-17-13(20)6-12(7-14(17)21)29-18(30)28-11-4-2-3-10(5-11)19(22,23)24/h2-9H,1H3,(H,25,26,27)(H2,28,29,30)
InChI Key QOQADIYOLOHRAW-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
GSK329 was designed to be selective for TNNI3K compared to VEGFR2, p38α, and BRaf [1]. It is 40-fold more selective for human TNNI3K compared to VEGFR2, 80-fold selective against p38α, and and >200-fold selective against B-Raf.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
TNNI3 interacting kinase Hs Inhibitor Inhibition 9.3 pKi - 1
⤷ pKi 9.3 (Ki 5.4x10-10 M) [1]
TNNI3 interacting kinase Mm Inhibitor Inhibition 7.9 pKi - 1
⤷ pKi 7.9 (Ki 1.3x10-8 M) [1]
TNNI3 interacting kinase Hs Inhibitor Inhibition 8.0 pIC50 - 1
⤷ pIC50 8.0 (IC50 1x10-8 M) [1]
B-Raf proto-oncogene, serine/threonine kinase Hs Inhibitor Inhibition <5.7 pIC50 - 1
⤷ pIC50 <5.7 (IC50 >2x10-6 M) [1]