Isocitrate dehydrogenase [NADP], cytoplasmic (IDH1)

Isocitrate dehydrogenase 1 (IDH1) is an enzyme that catalyzes the reversible NADP(+)-dependent conversion of isocitrate to α-ketoglutarate (α-KG), producing NADPH. Mutations in IDH1, most commonly at residue R132, are frequently found in various cancers. These mutations confer a neomorphic enzymatic activity: mutant IDH1 reduces α-KG to D-2-hydroxyglutarate (D-2HG), an oncometabolite implicated in tumorigenesis. Accumulation of D2HG disrupts cellular differentiation by interfering with enzymes such as TET family DNA hydroxylases and histone demethylases.

Other names

Isocitrate dehydrogenase 1

Inhibition of mutant IDH1 enzymatic activity, leading to decreased D-2-hydroxyglutarate (D2HG) production and subsequent reversal of epigenetic dysregulation.