GKT136901   Click here for help

GtoPdb Ligand ID: 9935

Synonyms: compound 67 [PMID: 20942471] | GKT 136901 | GKT-136901
Compound class: Synthetic organic
Comment: GKT136901 was identified as a lead compound in a high-throughput screening and medicinal chemistry campaign that was designed to identify novel NOX4-selective inhibitors [1]. It is an orally active compound that is suitable for investigating the preclinical potential of NOX4 inhibitors for the treatment of fibrotic diseases and cancers in which NOX4 activity has been implicated.
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 72.16
Molecular weight 366.09
XLogP 3.78
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES Clc1ccccc1n1[nH]c2c(c1=O)c(C)n(c(=O)c2)Cc1ccccn1
Isomeric SMILES Clc1ccccc1n1[nH]c2c(c1=O)c(C)n(c(=O)c2)Cc1ccccn1
InChI InChI=1S/C19H15ClN4O2/c1-12-18-15(10-17(25)23(12)11-13-6-4-5-9-21-13)22-24(19(18)26)16-8-3-2-7-14(16)20/h2-10,22H,11H2,1H3
InChI Key DNKYHHFCPXKFIY-UHFFFAOYSA-N
Bioactivity Comments
GKT136901 is selective for NOX4 and NOX1, compared to NOX2 [1]. It has no hERG liability (0% inhibition at 1 μM), and limited CYP450 enzyme liability (CYP3A4 IC50 >20 μM, and CYP1A, CYP2C19, CYP2C9 and CYP2D6 IC50s all >25 μM).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
NADPH oxidase 1 Primary target of this compound Hs Inhibitor Inhibition 6.8 pKi - 1
⤷ pKi 6.8 (Ki 1.6x10-7 M) [1]
Description: Cell free assay of ROS production by NOX1 membranes.
NADPH oxidase 4 Primary target of this compound Hs Inhibitor Inhibition 6.8 pKi - 1
⤷ pKi 6.8 (Ki 1.65x10-7 M) [1]
Description: Cell free assay of ROS production by NOX4 membranes.
cytochrome b-245 beta chain Hs Inhibitor Inhibition 5.8 pKi - 1
⤷ pKi 5.8 (Ki 1.53x10-6 M) [1]
Description: Cell free assay of ROS production by NOX2 membranes.