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Target intelligence / Profile preview
Isocitrate Dehydrogenase (IDH)
- Target
- IDH
- Molecular classification
- Enzyme, Oxidoreductase
01
Overview
Isocitrate dehydrogenase (IDH) is a key metabolic enzyme catalyzing the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, producing carbon dioxide and NADH or NADPH. IDH exists as multiple isoforms (IDH1, IDH2, IDH3) with distinct localizations and cofactor preferences. Mutations in IDH1 and IDH2 are frequently observed in cancers, resulting in neomorphic activity and production of the oncometabolite D-2-hydroxyglutarate. Mutant IDH enzymes are therapeutic targets, and inhibitors have been developed to treat specific cancers.
- Other names
- Isocitric dehydrogenaseIsocitrate dehydrogenase (NADP+)Isocitrate dehydrogenase (NAD+)
02
Mechanism of action
Inhibition of mutant IDH enzymes, leading to decreased production of D-2-hydroxyglutarate and promotion of cellular differentiation
03
Biological functions
Tricarboxylic acid cycle (TCA cycle)Krebs cycleCitric acid cycleMetabolic processRedox homeostasisBiosynthetic pathway supportNADPH productionNADH production
04
Disease associations
CancerGliomaLeukemiaMetabolic disorders
05
Safety considerations
Differentiation syndromeQT prolongationAdverse events related to specific inhibitors
06
Interacting drugs
IDH1 inhibitors (e.g., Ivosidenib, Olutasidenib)
1 more in the full profile.
07
Biomarkers
IDH1 mutation statusIDH2 mutation statusD-2-hydroxyglutarate levels
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