AGI-6780 - Isocitrate Dehydrogenase (IDH) 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAGI-6780Cat. No.: HY-15734CAS No.: 1432660-47-3分式: CHFNOS分量: 481.51作靶點: Isocitrate Dehydrogenase (IDH)作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 29 mg/mL

2、(60.23 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.0768 mL 10.3840 mL 20.7680 mL5 mM 0.4154 mL 2.0768 mL 4.1536 mL10 mM 0.2077 mL 1.0384 mL 2.0768 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 AGI-6780 有效且選擇性抑制腫瘤相關(guān)突變體 IDH2R14

3、0Q，IC50 為 231.7 nM。AGI-6780 對 IDH2WT 的作效果微弱，IC50 為 1908.1 nM。IC50 & Target IC50: 231.7 nM (IDH2R140Q), 1908.1 nM (IDH2WT) 1體外研究AGI-6780 is tested in both human glioblastoma U87 and TF-1 cells expressing IDH2R140Q, as well as1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEagainst IDH1R132H for 48 h

4、incubation, with IC50 of 112.6 nM, 180.51 nM, and 1 mM,respectivly.Treatment of TF-1R140Q cells with AGI-6780, at concentrations that lower 2HG to near-normalphysiologic levels, restore expression of both HBG and KLF1 genes and the color change associated withdifferentiation. AGI-6780 can reverse th

5、e IDH2R140Q-induced differentiation block in TF-1 cells.Pretreatment with AGI-6780 (0.2 M and 1 M) markedly decreased the intracellular concentration of (R)-2-hydroxyglutarate in the TF1R140Q cells and restored their ability to undergo EPO-induced differentiation 1.PROTOCOLKinase Assay 1 AGI-6780 is

6、 prepared as 10 mM stock in DMSO and diluted to 50X final concentration in DMSO, for a 50 Lreaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate is measured usinga NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction w

7、iththe addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportionto the amount of NADPH remaining. IDH enzyme activity in the direction of isocitrate to alpha-ketoglutarateconversion is measured by direct coupling of the NADPH production to conversion

8、of resazurin to resorufinby diaphorase. In both cases, resorufin is measured fluorometrically at Ex544 Em590 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cells are sorted from fresh or frozen bone marrow aspirates and blood samples aft

9、er labelling with PE-CD34,APC-CD38, PE-CD14, FITC-CD3 (clone HIT3a) and PECy7-CD19 (clone SJ25C1) antibodies using aMoFlow cell sorter. Unfractionated nucleated blood or bone marrow cells are plated in Methocult H4434methylcellulose medium at 104 cells/dish, in duplicate dishes per condition. AGI-67

10、80 (5 mM) is directlyadded to the medium. Dishes are incubated in a humidified incubator at 37C and colonies containing at least30 cells are counted after 13 days 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Clin Cancer Res. 2018 Apr 1;

11、24(7):1705-1715. Oncol Rep. 2018 Aug;40(2):635-646. Methods Mol Biol. 2018;1711:351-398.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Wang F, et al. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science. 2013 May 3;340(6132):622-6.McePdfHeightCaution: Product has not