| Name | AGI-6780 |
| Description | AGI-6780 is a potent and selective inhibitor of IDH2 R140Q mutant. |
| Cell Research | AGI-6780 is dissolved in DMSO and stored, and then diluted with appropriate media before use[1]. Cells are sorted from fresh or frozen bone marrow aspirates and blood samples after labelling with PE-CD34, APC-CD38, PE-CD14, FITC-CD3 (clone HIT3a) and PECy7-CD19 (clone SJ25C1) antibodies using a MoFlow cell sorter. Unfractionated nucleated blood or bone marrow cells are plated in Methocult H4434 methylcellulose medium at 104 cells/dish, in duplicate dishes per condition. AGI-6780 (5 mM) is directly added to the medium. Dishes are incubated in a humidified incubator at 37°C and colonies containing at least 30 cells are counted after 13 days[1]. |
| Kinase Assay | AGI-6780 is prepared as 10 mM stock in DMSO and diluted to 50X final concentration in DMSO, for a 50 μL reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH enzyme activity in the direction of isocitrate to alpha-ketoglutarate conversion is measured by direct coupling of the NADPH production to conversion of resazurin to resorufin by diaphorase. In both cases, resorufin is measured fluorometrically at Ex544 Em590[1]. |
| In vivo | AGI-6780 reverses differentiation blockage induced by IDH2/R140Q in TF-1 cells and induces rapid differentiation in primary samples from patients with IDH2/R140Q AML. It effectively reduces the levels of (R)-2-hydroxyglutarate (2-HG) in cell lines overexpressing ectopic IDH2/R140Q, with an EC50 of 20 nM, demonstrating excellent selectivity compared to other dehydrogenases. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 3.3 mg/mL (6.85 mM), Sonication is recommended.
DMSO : 125 mg/mL (259.6 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 89 mg/mL (184.84 mM), Sonication is recommended.
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| Keywords | IsocitrateDehydrogenase(IDH) | IsocitrateDehydrogenase | Isocitrate Dehydrogenase (IDH) | Isocitrate Dehydrogenase | Inhibitor | inhibit | IDH2 R140Q mutant | IDH | AGI-6780 | AGI6780 | AGI 6780 |
| Inhibitors Related | Disulfiram | Mycophenolate Mofetil | Rotenone | Ribavirin | 18β-Glycyrrhetinic acid | Benzyl alcohol | 2-Methylaminoethanol | Methotrexate disodium | Dimethyl malonate | Isomalt | D-Mannitol | Ethyl potassium malonate |
| Related Compound Libraries | Highly Selective Inhibitor Library | Bioactive Compound Library | Anti-Cancer Metabolism Compound Library | Inhibitor Library | NO PAINS Compound Library | Metabolism Compound Library | Bioactive Compounds Library Max | Covalent Inhibitor Library | Fluorochemical Library | Anti-Metabolism Disease Compound Library | Anti-Liver Cancer Compound Library | Anti-Cancer Active Compound Library |
United States
