Telaglenastat (CB-839)

Catalog No.S7655

For research use only.

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.

Telaglenastat (CB-839) Chemical Structure

CAS No. 1439399-58-2

Selleck's Telaglenastat (CB-839) has been cited by 52 publications

Purity & Quality Control

Choose Selective Glutaminase Inhibitors

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MDA-MB-231 cells M3;3R2N6fG:2b4jpZ4l1gSCjc4PhfS=> MmKyOkBl[Xm| M2Hve2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1FSS2PQj2yN|Eh[2WubIOgcYVie3W{ZXSgc44hPnSqIHThfUBjgSCqZX3vZ5l1d22ndIL5MEBKSzVyPUCuNFM{KM7:TR?= M2DM[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4OUi4PFA{Lz5{Nkm4PFgxOzxxYU6=
TNBC cell lines M2ftPWdzd3e2aDDpcohq[mm2b36gZZN{[Xl? MW[xJO69VQ>? NVTYVYdTPCCmYYnz NGHsWGNESi16M{mgeJJm[XSvZX70JIlv\HWlZXSgZ4VtdCCub4PzJI9zKGSnY4LlZZNm\CClZXzsJJBzd2yrZnXyZZRqd25iYomgcY9z\SC2aHHuJFUxLSCrbjDzbZgh[2WubDDsbY5meyBqSFPDNVgxPixiSFPDNVE1OyxiSFPDN|gtKE2GQT3NRk01OzZuIF3ERU1OSi1{M{GgZY5lKEi|NUe4WEk8KHSqZTDveIhmeiC|aYigZ4VtdCCuaX7ld{ApUEOFMUmzO{whUEOFN{CsJGJVPTR7LDDNSGEuVUJvMUW3MEBOTEFvTVKtOFU{KGGwZDDNSGEuVUJ2NkipJJdmemViZXn0bIVzKG6xdDDh[oZm[3SnZDDvdkBp[WRidHjlbZIh[2WubDDwdo9tcW[ncnH0bY9vKGGoZnXjeIVlKGK7IHzld5MhfGijbjC1NEUh[W6mIIfldoUh[2GubHXkJJJme2m|dHHueE4> MkDHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzFyNECxPFEoRjNzMESwNVgyRC:jPh?=
MM.1S BzR cells NGXPc2JHfW6ldHnvckBie3OjeR?= M1q0fVUh|ryP NYHobHU6OTZiaH;1dpM> MYX0doVifG2nboSge4l1cCCFQj24N|khe2mpbnnmbYNidnSueTDy[ZBz\XO|ZXSgc5h6\2WwIHPvcpN2dXC2aX;uJJJifGViaX6gdJJwfGWjc3;t[U1qdmirYnn0c5IhemW|aYP0ZY51KGOnbHzzMi=> M122OFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NEG1O|gzLz5{OESxOVc5OjxxYU6=
MM.1S cells M4[xSGNmdGxidnnhZoltcXS7IHHzd4F6 NIXkW|k4OiCqb4Xydy=> MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDRzNUe4Nkc,Ojh2MUW3PFI9N2F-
U266 cell lines MmPyR4VtdCC4aXHibYxqfHliYYPzZZk> Mkn6O|IhcG:3coO= NInYdG09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OESxOVc5Oid-Mki0NVU4QDJ:L3G+
HT1080 NEG5PYpEgXSxdH;4bYNqfHliYYPzZZk> MVW0PEBp NVHWUWx7UUN3MDC9JFQ1NjN6IN88US=> M4\0eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MUe0NVA2Lz5{OEG3OFExPTxxYU6=
HCC827 NXHnbGZkS3m2b4TvfIlkcXS7IHHzd4F6 MkXQTWM2OCB;IEWxMlQzKM7:TR?= NI\wTYQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEG3OFExPSd-MkixO|QyODV:L3G+
Assay
Methods Test Index PMID
Western blot collagen I/collagen III 29019707
Growth inhibition assay Cell growth 28967864
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 Research:

[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 Research:

[1]

  • Animal Models: Female Scid/Bg mice bearing TNBC or JIMT-1 xenograft
  • Dosages: 200 mg/kg
  • Administration: p.o.

Solubility (25°C)

In vitro

DMSO 100 mg/mL warmed
(174.95 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5% DMSO+corn oil
For best results, use promptly after mixing.

3mg/mL

Chemical Information

Molecular Weight 571.57
Formula

 C26H24F3N7O3S

CAS No. 1439399-58-2
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=CC=NC(=C1)CC(=O)NC2=NN=C(S2)CCCCC3=NN=C(C=C3)NC(=O)CC4=CC(=CC=C4)OC(F)(F)F

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04250545 Recruiting Drug: Sapanisertib|Drug: Telaglenastat Hydrochloride Leptomeningeal Neoplasm|Metastatic Lung Non-Small Cell Carcinoma|Metastatic Malignant Neoplasm in the Brain|Recurrent Lung Non-Small Cell Carcinoma|Stage IV Lung Cancer AJCC v8|Stage IVA Lung Cancer AJCC v8|Stage IVB Lung Cancer AJCC v8 National Cancer Institute (NCI) November 9 2020 Phase 1
NCT03875313 Terminated Drug: CB-839|Drug: Talazoparib Solid Tumor|Clear Cell Renal Cell Carcinoma|TNBC - Triple-Negative Breast Cancer|Colorectal Cancer|CRC|RCC|ccRCC Calithera Biosciences Inc May 20 2019 Phase 1|Phase 2
NCT02944435 Completed Drug: CB-839 Capsules|Drug: CB-839 Tablets Healthy Volunteers Calithera Biosciences Inc October 2016 Phase 1
NCT02771626 Completed Drug: CB-839|Drug: Nivolumab Clear Cell Renal Cell Carcinoma (ccRCC)|Melanoma|Non-small Cell Lung Cancer (NSCLC) Calithera Biosciences Inc August 1 2016 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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