Telaglenastat (CB-839)

Catalog No.S7655 Batch:S765508

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Technical Data

Formula

 C26H24F3N7O3S
Molecular Weight 571.57 CAS No. 1439399-58-2
Solubility (25°C)* In vitro DMSO 100 mg/mL (174.95 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Telaglenastat (CB-839) is a potent, selective, and orally bioavailable glutaminase inhibitor with IC50 of 24 nM for recombinant human GAC. CB-839(Telaglenastat) inudces autophagy and has antitumor activity. Phase 1.
Targets
Glutaminase [1]
(Cell-free assay)
24 nM
In vitro CB-839 exhibits time-dependent and slowly reversible kinetics. IC50 values for glutaminase inhibition by CB-839 following preincubation with rHu-GAC for-1 hour are < 50 nmol/L, at least 13-fold lower than with BPTES. CB-839 has antiproliferative activity in a triple-negative breast cancer (TNBC) cell line, HCC-1806, while no antiproliferative activity is observed in an estrogen receptor–positive cell line, T47D.[1]
In vivo In the mouse TNBC model, single agent CB-839 (200 mg/kg, p.o.) suppresses tumor growth by 61% relative to vehicle control. In the mouse JIMT-1 xenograft model, CB-839 alone (200 mg/kg, p.o.) results in 54% tumor growth inhibition (TGI) relative to vehicle control, combination of CB-839 (200 mg/kg, p.o.) with paclitaxel (10 mg/kg, p.o.) largely suppresses the regrowth of the tumors resulting in a TGI relative to vehicle control of 100%.[1]

Protocol (from reference)

Kinase Assay:

[1]
  • Inhibition of CB-839 on rHu-GAC

    The enzymatic activity is measured in assay buffer containing 50 mM Tris-Acetate pH 8.6, 150 mM K2HPO4 , 0.25 mM EDTA, 0.1 mg/mL bovine serum albumin, 1 mM DTT, 2 mM NADP+ and 0.01% Triton X-100. To measure inhibition, the inhibitor (prepared in DMSO) is first pre-mixed with glutamine and glutamate dehydrogenase (GDH) and reactions are initiated by the addition of rHu-GAC. Final reactions contains 2 nM rHu-GAC, 10 mM glutamine, 6 units/mL GDH and 2% DMSO. Generation of NADPH is monitored by fluorescence (Ex340/Em460 nm) every minute for 15 minutes on a SpectraMax M5e plate reader. Relative fluorescence units (RFU) are converted to units of NADPH concentration (µM) using a standard curve of NADPH. Each assay plate incorporates control reactions that monitores the conversion of glutamate (1 to 75 µM) plus NADP+ to α-ketoglutarate plus NADPH by GDH. Under these assay conditions, up to 75 µM glutamate is stoichiometrically converts to α-ketoglutarate/NADPH by GDH. Initial reaction velocities are calculated by fitting the first 5 minutes of each progress curve to a straight line. Inhibition curves are fitted to a four-parameter dose response equation of the form: % activity = Bottom + (Top-Bottom)/(1+10^((LogIC50-X)*HillSlope)).
Cell Assay:

[1]
  • Cell lines

    HCC1806, MDA-MB-231, and T47D cells

  • Concentrations

    0.1-1000 nM

  • Incubation Time

    72 h

  • Method

    For viability assays, all cell lines are treated with CB-839 at the indicated concentrations for 72 hours and analyzed for antiproliferative effects using Cell Titer Glo.
Animal Study:

[1]
  • Animal Models

    Female Scid/Bg mice bearing TNBC or JIMT-1 xenograft

  • Dosages

    200 mg/kg

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , Haematologica, 2018, doi:10.3324/haematol.2018.204701]

Data from [Data independently produced by , , Br J Cancer, 2018, 118(8):1074-1083]

Data from [Data independently produced by , , Biochem Pharmacol, 2018, 156:204-214]

Data from [Data independently produced by , , Tumor Biol, 2016, 37:11007-11015.]

Selleck's Telaglenastat (CB-839) has been cited by 92 publications

Targeting metabolic adaptive responses induced by glucose starvation inhibits cell proliferation and enhances cell death in osimertinib-resistant non-small cell lung cancer (NSCLC) cell lines [ Biochem Pharmacol, 2024, S0006-2952(24)00144-8] PubMed: 38522556
ERK5 Interacts with Mitochondrial Glutaminase and Regulates Its Expression [ Int J Mol Sci, 2024, 25(6)3273] PubMed: 38542254
RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis [ Signal Transduct Target Ther, 2023, 8(1):159] PubMed: 37080995
An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression [ Cancer Discov, 2023, 13(7):1696-1719] PubMed: 37140445
Histone Deacetylase 6 Inhibition Exploits Selective Metabolic Vulnerabilities in LKB1 Mutant, KRAS Driven NSCLC [ J Thorac Oncol, 2023, S1556-0864(23)00197-1] PubMed: 36958689
Immuno-metabolic dendritic cell vaccine signatures associate with overall survival in vaccinated melanoma patients [ Nat Commun, 2023, 10.1038/s41467-023-42881-4] PubMed: 37938561
Alanine supplementation exploits glutamine dependency induced by SMARCA4/2-loss [ Nat Commun, 2023, 14(1):2894] PubMed: 37210563
SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells [ Nat Commun, 2023, 14(1):3673] PubMed: 37339981
Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2-positive gastric cancer [ Cancer Commun (Lond), 2023, 43(8):909-937] PubMed: 37434399
Lipophagy-mediated cholesterol synthesis inhibition is required for the survival of hepatocellular carcinoma under glutamine deprivation [ Redox Biol, 2023, 63:102732] PubMed: 37150151

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