ArticleThe Biochemical journal2018
Inhibitor potency varies widely among tumor-relevant human isocitrate dehydrogenase 1 mutants.
Article in The Biochemical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models.The Journal of biological chemistry · 2025Article
- Active site remodeling in tumor-relevant IDH1 mutants drives distinct kinetic features and potential resistance mechanisms.Nature communications · 2024Article
- Active site remodeling in tumor-relevant IDH1 mutants drives distinct kinetic features and potential resistance mechanisms.bioRxiv : the preprint server for biology · 2024Article
- Capturing the Dynamic Conformational Changes of Human Isocitrate Dehydrogenase 1 (IDH1) upon Ligand and Metal Binding Using Hydrogen-Deuterium Exchange Mass Spectrometry.Biochemistry · 2023Article
- Probing altered enzyme activity in the biochemical characterization of cancer.Bioscience reports · 2022Review
- Isocitrate dehydrogenase gene variants in cancer and their clinical significance.Biochemical Society transactions · 2021Review
- Targeting Mitochondrial Oncometabolites: A New Approach to Overcome Drug Resistance in Cancer.Pharmaceutics · 2021Review
- Evaluating Mechanisms of IDH1 Regulation through Site-Specific Acetylation Mimics.Biomolecules · 2021Article
- 2-Hydroxyglutarate in Cancer Cells.Antioxidants & redox signaling · 2020Review
- An acidic residue buried in the dimer interface of isocitrate dehydrogenase 1 (IDH1) helps regulate catalysis and pH sensitivity.The Biochemical journal · 2020Article
- Water Networks and Correlated Motions in Mutant Isocitrate Dehydrogenase 1 (IDH1) Are Critical for Allosteric Inhibitor Binding and Activity.Biochemistry · 2020Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Mutations in isocitrate dehydrogenase 1 (IDH1) drive most low-grade gliomas and secondary glioblastomas and many chondrosarcomas and acute myeloid leukemia cases. Most tumor-relevant IDH1 mutations are deficient in the normal oxidization of isocitrate to α-ketoglutarate (αKG), but gain the neomorphic activity of reducing αKG to D-2-hydroxyglutarate (D2HG), which drives tumorigenesis. We found previously that IDH1 mutants exhibit one of two reactivities: deficient αKG and moderate D2HG production (including commonly observed R132H and R132C) or moderate αKG and high D2HG production (R132Q). Here, we identify a third type of reactivity, deficient αKG and high D2HG production (R132L). We show that R132Q IDH1 has unique structural features and distinct reactivities towards mutant IDH1 inhibitors. Biochemical and cell-based assays demonstrate that while most tumor-relevant mutations were effectively inhibited by mutant IDH1 inhibitors, R132Q IDH1 had up to a 16 300-fold increase in IC
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