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Target intelligence / Profile preview
Isocitrate Dehydrogenase [NADP(+)] Cytoplasmic (IDH1)
- Target
- IDH1
- Molecular classification
- Enzyme
01
Overview
Isocitrate dehydrogenase 1 (IDH1) is a cytosolic and peroxisomal enzyme that catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG), producing NADPH. This reaction is crucial for biosynthetic pathways, redox balance, and cellular defense against oxidative stress. Mutations in IDH1, particularly R132, are common in cancers like glioma and AML. These mutations lead to the production of D-2-hydroxyglutarate (D2HG), an oncometabolite that disrupts normal cell differentiation.
02
Mechanism of action
IDH1 inhibitors block the mutant IDH1 enzyme activity, preventing the production of D-2-hydroxyglutarate (D2HG)
03
Biological functions
Oxidative decarboxylationNADPH productionRedox balanceLipid metabolism supportAntioxidant defenseGlucose sensing
04
Disease associations
CancerGlioma susceptibilityEnchondromatosis/Ollier typeMaffucci syndrome
05
Safety considerations
Differentiation syndromeQTc prolongation
06
Biomarkers
IDH1 R132 mutationsD-2-hydroxyglutarate (D2HG) levels
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