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].

TEPP-46 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 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

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 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

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/)
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]