受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C26H24F3N7O3S |
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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) |
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* <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. |
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. |
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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 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] |
キナーゼアッセイ | Inhibition of CB-839 on rHu-GAC | |
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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 CB-839 at the indicated concentrations for 72 hours and analyzed for antiproliferative effects using Cell Titer Glo. |
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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. |
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]
HuR controls glutaminase RNA metabolism [ Nat Commun, 2024, 15(1):5620] | PubMed: 38965208 |
A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [ EBioMedicine, 2024, 102:105090] | PubMed: 38547578 |
Targeting the glutamine metabolism to suppress cell proliferation in mesenchymal docetaxel-resistant prostate cancer [ Oncogene, 2024, 43(26):2038-2050] | PubMed: 38750263 |
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 |
Mesenchymal Stem Cells Promote an Increase in Neuronal Oscillation via Glutamate Tonic Release [ Neuroscience, 2024, 552:76-88] | PubMed: 38909673 |
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 |
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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