A potent, selective inhibitor of mutant IDH2
AGI-6780 is a potent and selective inhibitor of tumor-associated IDH2/R140Q mutation with IC50 value of 23 nM [1].
AGI-6780 could significantly reduce intracellular concentration of 2HG in the human glioblastoma TF1/R140Q cells, as well as reverse IDH2/R140Q-mediated differentiation block in TF1 cells in the presence of EPO. AGI-6780 could restore KLF1 and hemoglobin G1/2 expressions in the EPO-induced TF1/R140Q cells [1].
参考文献:
[1] Wang F1,?Travins J,?DeLaBarre B,?Penard-Lacronique V,?Schalm S,?Hansen E,?Straley K,?Kernytsky A,?Liu W,?Gliser C,?Yang H,?Gross S,?Artin E,?Saada V,Mylonas E,?Quivoron C,?Popovici-Muller J,?Saunders JO,?Salituro FG,?Yan S,?Murray S,?Wei W,?Gao Y,?Dang L,?Dorsch M,?Agresta S,?Schenkein DP,?Biller SA,?Su SM,?de Botton S,?Yen KE. Targeted?inhibition?of?mutant?IDH2?in?leukemia?cells?induces?cellular?differentiation. Science.?2013 May 3;340(6132):622-6.
| Cell experiment [1]: | |
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Cell lines |
Primary human AML cells |
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Preparation method |
The solubility of this compound in DMSO is > 22.25 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
5 μM up to 10 days |
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Applications |
IDH2 mutant samples treated with AGI-6780 showed a dose-dependent reduction in the amounts of extracellular and intracellular (R)-2-hydroxyglutarate. In the presence AGI-6780, a burst of cell proliferation was also observed only in the IDH2/R140Q mutant samples. Furthermore, AGI-6780 did not exert a cytotoxic effect as the number of viable, more mature CD45-positive cells increased in the presence of AGI-6780 only in the IDH2/R140Q mutant samples whereas the IDH2/WT samples remained unchanged. |
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参考文献: [1] Wang F1,Travins J,DeLaBarre B,Penard-Lacronique V,Schalm S,Hansen E,Straley K,Kernytsky A,Liu W,Gliser C,Yang H,Gross S,Artin E,Saada V,Mylonas E,Quivoron C,Popovici-Muller J,Saunders JO,Salituro FG,Yan S,Murray S,Wei W,Gao Y,Dang L,Dorsch M,Agresta S,Schenkein DP,Biller SA,Su SM,de Botton S,Yen KE. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science.2013 May 3;340(6132):622-6. | |
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