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Target intelligence / Profile preview
Isocitrate dehydrogenase [NADP] cytoplasmic (IDH1)
- Target
- IDH1
- Molecular classification
- Enzyme
01
Overview
IDH1 is a key metabolic enzyme that catalyzes the reversible oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the cytoplasm and peroxisomes, using NADP+ as a cofactor and producing NADPH. Mutations in IDH1, particularly at R132, are common in certain cancers, leading to a neomorphic activity that produces the oncometabolite D-2-hydroxyglutarate, disrupting epigenetic regulation. Mutant IDH1 is a therapeutic target, with inhibitors like Ivosidenib approved for AML.
02
Mechanism of action
Inhibition of mutant IDH1 neomorphic activity, specifically the production of D-2-hydroxyglutarate
03
Biological functions
Reductive biosynthesisCellular antioxidant defenseGlucose sensingLipid metabolismβ-oxidation of unsaturated fatty acids
04
Disease associations
Cancer
05
Interacting drugs
Ivosidenib
06
Biomarkers
IDH1 mutation statusD-2-hydroxyglutarate (D-2HG) levels
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