A Highly Facile and Specific Assay for Cancer-Causing Isocitrate Dehydrogenase Mutant Using C-13(4)-Labeled alpha-Ketoglutarate and Heteronuclear NMR

초록

Isocitrate dehydrogenase mutations with neomorphic activity of converting a-ketoglutarate to 2-hydroxyglutarate have been found in many types of cancers. We report an NMR-based assay specific for the mutant using C-13(4)-labeled alpha-ketoglutarate. It can be done in a complex mixture without extraction, give time-dependent absolute quantitation, and be applied to enzyme inhibition studies. Its merits over conventional assays should facilitate inhibitor developments for a new class of target-oriented anticancer agents.

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