Stemcell, 100-0514, (2R)-Octyl-α-hydroxyglutarate

(2R)-Octyl-α-hydroxyglutarate is a cell-permeable derivative of α-hydroxyglutarate (2-HG). D- and L-2-hydroxyglutarate dehydrogenases convert 2-HG to α-ketoglutarate (αKG or 2-oxoglutarate), which, along with oxygen, are co-substrates for a large family of αKG-dependent dioxygenases. 2-HG itself inhibits αKG-dependent dioxygenases by competing with αKG for binding to this family of enzymes (Xu et al.). Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are associated with certain cancers (Reitman et al.; Sulkowski et al.). These enzymes convert isocitrate to 2-HG rather than αKG, and this results in high levels of accumulated 2-HG in cancer cells. (2R)-Octyl-α-hydroxyglutarate is useful for investigating oxidative mitochondrial processes of IDH mutations in cancer.

CANCER RESEARCH

· Inhibits αKG-dependent dioxygenases (Sulkowski et al.; Xu et al.).