telaglenastat   Click here for help

GtoPdb Ligand ID: 9053

Synonyms: CB-839 | CB839
PDB Ligand
Compound class: Synthetic organic
Comment: Telaglenastat (CB-839) is an investigational noncompetitive (allosteric) glutaminase inhibitor [1]. It is one of the structures claimed in patent US8604016 [2], where it is compound 670. The anti-cancer activity of CB-839 was first reported in preclinical studies in triple-negative breast cancer (TNBC) cells in vitro and in vivo [1].
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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

telaglenastat 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 9
Hydrogen bond donors 2
Rotatable bonds 15
Topological polar surface area 160.12
Molecular weight 571.16
XLogP 4.25
No. Lipinski's rules broken 1

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 O=C(Nc1ccc(nn1)CCCCc1nnc(s1)NC(=O)Cc1ccccn1)Cc1cccc(c1)OC(F)(F)F
Isomeric SMILES O=C(Nc1ccc(nn1)CCCCc1nnc(s1)NC(=O)Cc1ccccn1)Cc1cccc(c1)OC(F)(F)F
InChI InChI=1S/C26H24F3N7O3S/c27-26(28,29)39-20-9-5-6-17(14-20)15-22(37)31-21-12-11-18(33-34-21)7-1-2-10-24-35-36-25(40-24)32-23(38)16-19-8-3-4-13-30-19/h3-6,8-9,11-14H,1-2,7,10,15-16H2,(H,31,34,37)(H,32,36,38)
InChI Key PRAAPINBUWJLGA-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/)
No information available.
Summary of Clinical Use Click here for help
CB-839 is being evaluated in a Phase 1 clinical trial (NCT02071862) for activity against solid tumours. Tumours types being investigated are triple-negative breast cancer, non-small cell lung cancer (adenocarcinoma), renal cell cancer, mesothelioma, fumarate hydratase (FH)-deficient tumors, succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST), SDH-deficient non-GIST tumors, tumors harboring mutations in isocitrate dehydrogenase-1 (IDH1) or IDH2, and cMyc mutation tumors. Two further Phase 1 clinical trials are assessing CB-839 in hematological tumors (Non-Hodgkin's Lymphoma (NHL), multiple myeloma, Waldenstrom's macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL) and other B-cell NHL subtypes)- NCT02071888 and NCT02071927.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Many tumour cells are dependent on glutamine as an energy source for growth and survival. CB-839 inhibits glutaminase, the first enzyme in glutamine utilisation (glutaminolysis), thereby starving tumour cells of their energy source.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02071862 Study of the Glutaminase Inhibitor CB-839 in Solid Tumors Phase 1 Interventional Calithera Biosciences, Inc
NCT02071888 Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors Phase 1 Interventional Calithera Biosciences, Inc
NCT02071927 Study of the Glutaminase Inhibitor CB-839 in Leukemia Phase 1 Interventional Calithera Biosciences, Inc