Telaglenastat (CB-839)

製品コードS7655 バッチS765511

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

 C26H24F3N7O3S
分子量 571.57 CAS No. 1439399-58-2
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 100 mg/mL (174.95 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5% DMSO 95% Corn oil

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 0.250mg/ml (0.44mM) Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 CB-839 (Telaglenastat) 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.
in vitro

Telaglenastat (CB-839) exhibits time-dependent and slowly reversible kinetics. Its IC50 values for glutaminase inhibition following preincubation with rHu-GAC for-1 hour are < 50 nmol/L, at least 13-fold lower than with BPTES. This compound 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 Telaglenastat (CB-839) (200 mg/kg, p.o.) suppresses tumor growth by 61% relative to vehicle control. In the mouse JIMT-1 xenograft model, this compound alone (200 mg/kg, p.o.) results in 54% tumor growth inhibition (TGI) relative to vehicle control, while its combination with NSC 125973 (10 mg/kg, p.o.) largely suppresses the regrowth of the tumors, resulting in a TGI relative to vehicle control of 100%.[1]

プロトコル(参考用のみ)

キナーゼアッセイ 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 by Telaglenastat (CB-839), 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)).
細胞アッセイ 細胞株 HCC1806, MDA-MB-231, and T47D cells
濃度 0.1-1000 nM
反応時間 72 h
実験の流れ

For viability assays, all cell lines are treated with Telaglenastat (CB-839) at the indicated concentrations for 72 hours and analyzed for antiproliferative effects using Cell Titer Glo.
動物実験 動物モデル Female Scid/Bg mice bearing TNBC or JIMT-1 xenograft
投薬量 200 mg/kg
投与方法 p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/24523301/

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

High fructose consumption aggravates inflammation by promoting effector T cell generation via inducing metabolic reprogramming [ Signal Transduct Target Ther, 2025, 10(1):271] PubMed: 40854873
Chaperone-mediated autophagy directs a dual mechanism to balance premature senescence and senolysis to prevent intervertebral disc degeneration [ Bone Res, 2025, 13(1):62] PubMed: 40506462
GDH1-dependent α-ketoglutarate promotes HBV transcription by modulating histone methylations on the cccDNA minichromosome [ Clin Mol Hepatol, 2025, 10.3350/cmh.2024.0694] PubMed: 39905842
The metabolic shift of glutaminase 2 to glutaminase 1 promotes LGR5 + progenitor cell proliferation in liver cirrhosis [ Cell Mol Life Sci, 2025, 82(1):251] PubMed: 40550888
Endogenous protein S100A14 stabilizes glutaminase to render hepatocellular carcinoma resistant to sorafenib [ J Transl Med, 2025, 23(1):435] PubMed: 40217256
Autophagic flux-lipid droplet biogenesis cascade sustains mitochondrial fitness in colorectal cancer cells adapted to acidosis [ Cell Death Discov, 2025, 11(1):21] PubMed: 39856069
Imaging the uptake and metabolism of glutamine in prostate tumor models using CEST MRI [ Npj Imaging, 2025, 3(1):34] PubMed: 40750673
Distinct malignant cell states and myeloid glutamate signaling associated with aggressive pancreatic neuroendocrine tumors [ bioRxiv, 2025, 2025.07.15.664730] PubMed: 40791359
PP2A activation drives aberrant macropinocytosis and cell death in pancreatic ductal adenocarcinoma [ bioRxiv, 2025, 2025.07.14.664742] PubMed: 40791444
Macrophages excite muscle spindles with glutamate to bolster locomotion [ Nature, 2024, 10.1038/s41586-024-08272-5] PubMed: 39633045

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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