Variants of isocitrate dehydrogenase IDH 1 and 2 are known to alter the metabolism in cancer cells. Through a combined approach of X-ray crystallography and 1H NMR in collaboration with Christopher Schofield from University of Oxford, we reveal that 2OG derivatives can serve as substrates of the investigated IDH1/2 variants, but not of WT IDH1/2, and have the potential to act as 2OG-competitive inhibitors.

_{1 Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research}

_{2 Inorganic Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom}

_{3 Evotec (UK) Ltd, Abingdon, United Kingdom}

_{4 Evotec (US) Inc., Princeton, NJ, USA}