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    InvivoChem Cat #: V0862
    CAS #: 1432660-47-3Purity ≥98%

    Description: AGI-6780 (AGI6780; AGI 6780) is a potent and selective inhibitor of tumor-associated mutant IDH2 (isocitrate dehydrogenases 2) R140Q with potential anti-inflammatory activity. It inhibits IDH2 R140Q with an IC50 of 23 nM. It shows less potency against IDH2(WT) with an IC50 of 190±8.1 nM. 

    References: Science. 2013 May 3;340(6132):622-6.

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    Molecular Weight (MW)481.51
    CAS No.1432660-47-3
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 96 mg/mL (199.4 mM)
    Water: <1 mg/mL
    Ethanol: 96 mg/mL (199.4 mM)
    SMILES O=S(C1=CC=C(C2=CSC=C2)C(NC(NC3=CC=CC(C(F)(F)F)=C3)=O)=C1)(NC4CC4)=O
    SynonymsAGI 6780; AGI-6780;; AGI6780; N-cyclopropyl-4-(thiophen-3-yl)-3-(3-(3-(trifluoromethyl)phenyl)ureido)benzenesulfonamide

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    In Vitro

    In vitro activity: AGI-6780 potently reduce (R)-2-hydroxyglutarate (2HG) levels in cell lines ectopically overexpressing IDH2/R140Q with EC50 of 20 nM, with excellent selectivity against other dehydrogenases. AGI-6780 reverses the IDH2/R140Q-induced differentiation block in TF-1 cells, and induces blast differentiation in primary human IDH2/R140Q AML patient samples.

    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.

    Cell Assay: 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.

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    ReferencesScience. 2013 May 3;340(6132):622-6.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


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