ZAK inhibitor 6p   Click here for help

GtoPdb Ligand ID: 10402

Compound class: Synthetic organic
Comment: This compound is reported as a potent, selective and orally active inhibitor of sterile alpha motif and leucine zipper containing kinase (ZAK) [1]. It exhibits predicted antihypertrophic cardiomyopathy (HCM) efficacy in vivo in a spontaneous hypertensive rat (SHR) model.
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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 7
Topological polar surface area 135.54
Molecular weight 559.12
XLogP 6.28
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 COc1n[nH]c2c1cc(cn2)c1nnn(c1)c1c(F)ccc(c1F)NS(=O)(=O)c1cccc(c1)c1ccccc1
Isomeric SMILES COc1n[nH]c2c1cc(cn2)c1nnn(c1)c1c(F)ccc(c1F)NS(=O)(=O)c1cccc(c1)c1ccccc1
InChI InChI=1S/C27H19F2N7O3S/c1-39-27-20-13-18(14-30-26(20)32-33-27)23-15-36(35-31-23)25-21(28)10-11-22(24(25)29)34-40(37,38)19-9-5-8-17(12-19)16-6-3-2-4-7-16/h2-15,34H,1H3,(H,30,32,33)
InChI Key QRDCOOSKIFYKIQ-UHFFFAOYSA-N
Bioactivity Comments
A KINOMEscan® screen identified abelson murine leukemia viral oncogene homolog 1 (ABL1), B lymphoid tyrosine kinase (BLK), FMS like tyrosine kinase 3 (FLT3 ITD, F691L), lymphocyte-specific protein tyrosine kinase (LCK), LIM domain kinase 1 (LIMK1), LIM domain kinase 2 (LIMK2) and receptor-interacting serine/threonine-protein kinase 2 (RIPK2) as off-targets of compound 6p (all inhibited >90% by 1μM compound) [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
ZAK sterile alpha motif and leucine zipper containing kinase AZK Primary target of this compound Hs Inhibitor Inhibition 8.1 pKd - 1
⤷ pKd 8.1 (Kd 8x10-9 M) [1]
Description: Binding affinity determined using an active site-dependent competition binding assay.
ABL proto-oncogene 1, non-receptor tyrosine kinase Hs Inhibitor Inhibition 7.8 pKd - 1
⤷ pKd 7.8 (Kd 1.5x10-8 M) [1]
LIM domain kinase 1 Hs Inhibitor Inhibition 7.6 pKd - 1
⤷ pKd 7.6 (Kd 2.3x10-8 M) [1]
receptor interacting serine/threonine kinase 2 Hs Inhibitor Inhibition 7.2 pKd - 1
⤷ pKd 7.2 (Kd 5.7x10-8 M) [1]
LIM domain kinase 2 Hs Inhibitor Inhibition 7.2 pKd - 1
⤷ pKd 7.2 (Kd 6.3x10-8 M) [1]
LCK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.8 pKd - 1
⤷ pKd 6.8 (Kd 1.6x10-7 M) [1]
BLK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.7 pKd - 1
⤷ pKd 6.7 (Kd 1.9x10-7 M) [1]
ABL proto-oncogene 1, non-receptor tyrosine kinase Hs Inhibitor Inhibition 8.4 pIC50 - 1
⤷ pIC50 8.4 (IC50 4x10-9 M) [1]
Description: Inhibition of enzymatic activity determined in a ADP-GloTM assay.
ZAK sterile alpha motif and leucine zipper containing kinase AZK Hs Inhibitor Inhibition 8.4 pIC50 - 1
⤷ pIC50 8.4 (IC50 4x10-9 M) [1]
Description: Inhibition of enzymatic activity determined in a ADP-GloTM assay.