compound 3k [PMID: 28688274]   Click here for help

GtoPdb Ligand ID: 13523

Compound class: Synthetic organic
Comment: This compound is reported as an inhibitor of the tumour cell specific isoform of pyruvate kinase, PKM2 [2]. Compound 3k has been used to demonstrate the potential of SIRT1 (deacetylates PKM2 and reduces its activity) and PKM2 as therapeutic targets for the reduction of lactate production in the brain as a mechanism to slow progression of parkinsonism [1].
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

compound 3k [PMID: 28688274] is commercially available from our sponsors

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 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.

✖
Hydrogen bond acceptors 3
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 94.77
Molecular weight 345.48
XLogP 2.34
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
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.

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/)

✖
Canonical SMILES CC1=C(CSC(=S)N2CCCCC2)C(=O)C3=C(C=CC=C3)C1=O
Isomeric SMILES S=C(N1CCCCC1)SCC=2C(=O)C3=C(C(C2C)=O)C=CC=C3
InChI InChI=1S/C18H19NO2S2/c1-12-15(11-23-18(22)19-9-5-2-6-10-19)17(21)14-8-4-3-7-13(14)16(12)20/h3-4,7-8H,2,5-6,9-11H2,1H3
InChI Key STAFOGVMELKGRI-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 3k inhibits PKM1 with an in vitro IC50 >16 μM, i.e. ~6-fold selectivity for PKM2 over PKM1 [2]. It has antiproliferative/cytotoxic effects in high PKM2-expressing human cancer cell lines.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
pyruvate kinase M1/2 Hs Inhibitor Inhibition 5.5 pIC50 - 2
⤷ pIC50 5.5 (IC50 2.95x10-6 M) [2]
Description: Inhibition of PKM2 catalysis in a fluorescent PK-LDH coupled assay.