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Isocitrate Dehydrogenase 1 R132H (IDH1 R132H)
- Target
- IDH1 R132H
- Molecular classification
- Enzyme, Metabolic enzyme, Oxidoreductase
01
Overview
Isocitrate Dehydrogenase 1 R132H (IDH1 R132H) is a specific mutation of the IDH1 enzyme where the amino acid arginine at position 132 is replaced with histidine. This mutation results in a neomorphic enzyme activity, converting α-KG to D-2-hydroxyglutarate (D-2HG), an oncometabolite. This leads to accumulation of D-2HG, inhibition of α-KG-dependent dioxygenases, widespread changes in histone and DNA methylation, and impaired cellular differentiation. It is a diagnostic marker and therapeutic target, particularly in gliomas and acute myeloid leukemia.
- Other names
- IDH1 mutantR132H IDH1Mutant IDH1
02
Mechanism of action
Inhibition of the mutated IDH1 enzyme, preventing the production of D-2HG.
03
Biological functions
Catalyzes the conversion of isocitrate to alpha-ketoglutarate (α-KG) in wild-type formNeomorphic activity: converts α-KG to D-2-hydroxyglutarate (D-2HG) in mutant form
04
Disease associations
Low-grade gliomas (WHO Grades II and III)Secondary glioblastomasAcute myeloid leukemia (CN-AML)Oncogenesis
05
Safety considerations
Potential for off-target effects of IDH1 inhibitorsDevelopment of resistance to IDH1 inhibitors
06
Interacting drugs
Targeted inhibitors of mutant IDH1 (e.g., Ivosidenib, Enasidenib)
07
Biomarkers
IDH1 R132H mutation status for glioma diagnosis and prognosisD-2HG levels in vivo
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