Telaglenastat (CB-839)

製品コード：S7655 純度：99.95%

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.

CAS No. 1439399-58-2

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 56500	国内在庫あり
100mg	JPY 149500	国内在庫あり
1g	JPY 295500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（99）

製品安全説明書

現在のバッチを見る：純度： 99.95%

99.95

Telaglenastat (CB-839)関連製品

関連製品	BPTES 6-Diazo-5-oxo-L-norleucine JHU-083 GK921	もっと見る
関連化合物ライブラリー	FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Protease Inhibitor Library Ubiquitination Compound Library	もっと見る

Glutaminase阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
MM.1S BzR cells	Function assay	5 μM	16 hours	treatment with CB-839 significantly repressed oxygen consumption rate in proteasome-inhibitor resistant cells.	28415782
TNBC cell lines	Growth inhibiton assay	1 μM	4 days	CB-839 treatment induced cell loss or decreased cell proliferation by more than 50% in six cell lines (HCC1806, HCC1143, HCC38, MDA-MB-436, MDA-MB-231 and Hs578T); the other six cell lines (HCC1937, HCC70, BT549, MDA-MB-157, MDA-MB-453 and MDA-MB468) were either not affected or had their cell proliferation affected by less than 50% and were called resistant.	31040181
MDA-MB-231 cells	Cytotoxicity assay		6 days	Cytotoxicity against human MDA-MB-231 cells measured on 6th day by hemocytometry, IC50=0.033 μM	26988803
MM.1S cells	Cell viability assay		72 hours		28415782
U266 cell lines	Cell viability assay		72 hours		28415782
HT1080	Cytotoxicity assay		48 h	IC50 = 44.38 μM	28174105
HCC827	Cytotoxicity assay			IC50 = 51.42 μM	28174105
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Targets

Glutaminase ^[1]
(Cell-free assay)

24 nM

In Vitro
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]
Kinase Assay	Inhibition of CB-839 on rHu-GAC
Kinase Assay	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)).
細胞実験	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 CB-839 at the indicated concentrations for 72 hours and analyzed for antiproliferative effects using Cell Titer Glo.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	collagen I/collagen III		29019707
	Growth inhibition assay	Cell growth		28967864

In Vivo
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 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]
動物実験	動物モデル	Female Scid/Bg mice bearing TNBC or JIMT-1 xenograft
	投与量	200 mg/kg
	投与経路	p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT04250545	Recruiting	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)	October 26 2020	Phase 1
NCT02944435	Completed	Healthy Volunteers	Calithera Biosciences Inc	October 2016	Phase 1
NCT02071927	Completed	Acute Myeloid Leukemia (AML)\|Acute Lymphocytic Leukemia (ALL)	Calithera Biosciences Inc	March 2014	Phase 1

参考
[1] Gross MI, et al. Mol Cancer Ther. 2014, 13(4):890-901.

参考

[1] Gross MI, et al. Mol Cancer Ther. 2014, 13(4):890-901.

化学情報

分子量	571.57	化学式	C₂₆H₂₄F₃N₇O₃S
CAS No.	1439399-58-2	SDF	Download Telaglenastat (CB-839) SDFをダウンロードする
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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (174.95 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo Batch: Add solvents to the product individually and in order.					投与溶液組成計算機
	Clear solution	5% DMSO 1 95% Corn oil	0.25mg/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.	投与溶液組成計算機
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	0.5mg/ml (0.87mM)	Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil	0.8mg/ml (1.40mM)	Taking the 1 mL working solution as an example, add 50 μL of 16 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.

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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