Science Pool

Natural and synthetic 2-oxoglutarate derivatives are substrates for oncogenic variants of human isocitrate dehydrogenase 1 and 2

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.