TEPP-46   Click here for help

GtoPdb Ligand ID: 10555

Synonyms: compound 46 [PMID: 20451379] | ML-265 | ML265 | TEPP46
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: TEPP-46 is an activator of tumour-associated pyruvate kinase M2 (PKM2) [1,4-5]. It promotes formation of the highly active PKM2 tetramer, and reduces cancer cell proliferation by interfering with anabolic metabolism. It is active in a mouse xenograft model [4].
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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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Click here for structure editor
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 3
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 130.36
Molecular weight 372.07
XLogP 0.85
No. Lipinski's rules broken 0
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 Nc1cccc(c1)Cn1ncc2c(c1=O)n(C)c1c2sc(c1)S(=O)C
Isomeric SMILES Nc1cccc(c1)Cn1ncc2c(c1=O)n(C)c1c2sc(c1)S(=O)C
InChI InChI=1S/C17H16N4O2S2/c1-20-13-7-14(25(2)23)24-16(13)12-8-19-21(17(22)15(12)20)9-10-4-3-5-11(18)6-10/h3-8H,9,18H2,1-2H3
InChI Key ZWKJWVSEDISQIS-UHFFFAOYSA-N
References
1. Anastasiou D, Yu Y, Israelsen WJ, Jiang JK, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A et al.. (2012)
Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis.
Nat Chem Biol, 8 (10): 839-47. [PMID:22922757]
2. Angiari S, Runtsch MC, Sutton CE, Palsson-McDermott EM, Kelly B, Rana N, Kane H, Papadopoulou G, Pearce EL, Mills KHG et al.. (2020)
Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4+ T Cell Pathogenicity and Suppresses Autoimmunity.
Cell Metab, 31 (2): 391-405.e8. DOI: 10.1016/j.cmet.2019.10.015 [PMID:31761564]
3. Fan F, Wood KV. (2007)
Bioluminescent assays for high-throughput screening.
Assay Drug Dev Technol, 5 (1): 127-36. [PMID:17355205]
4. Jiang J, Walsh MJ, Brimacombe KR, Anastasiou D, Yu Y, Israelsen WJ, Hong BS, Tempel W, Dimov S, Veith H et al.. (2010)
ML265: A potent PKM2 activator induces tetramerization and reduces tumor formation and size in a mouse xenograft model.
Probe Reports from the NIH Molecular Libraries Program,. [PMID:23905203]
5. Jiang JK, Boxer MB, Vander Heiden MG, Shen M, Skoumbourdis AP, Southall N, Veith H, Leister W, Austin CP, Park HW et al.. (2010)
Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase.
Bioorg Med Chem Lett, 20 (11): 3387-93. [PMID:20451379]