ArticleCancer cell2011
Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases.
Article in Cancer cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,742 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1,742 citing papers in PubMed, 2,803 citations in OpenAlex.
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- Comutation of asxl1 and IDH2R172K enhances leukemogenesis and correlates with epigenetic activation of MAPK and AP-1 in zebrafish.Blood advances · 2026Article
- Genome-wide CRISPR screen identifies PKMYT1 inhibition as a synthetic lethal vulnerability in IDH1-mutant glioma.Cancer letters · 2026Article
- Immunogenic cell death: synergizing ferroptosis and cuproptosis to overcome immunotherapy resistance.Medical oncology (Northwood, London, England) · 2026Review
- Stable clocks, rewired rhythms: circadian remodeling in skeletal muscle during aging, cachexia, and type 2 diabetes.Life metabolism · 2026Review
- Depletion of the isocitrate dehydrogenase 3 subunit IDHA-1 licenses germ cell-to-neuron direct reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Methods for assessing binding of a small-molecule radioligand to soluble enzyme isocitrate dehydrogenase 1 variants.EJNMMI radiopharmacy and chemistry · 2026Article
- Glutamine Metabolism: a Metabolic Hub Linking Vascular Remodeling and Plaque Stability in Atherosclerosis.Current atherosclerosis reports · 2026Review
- Review
- TET2 loss triggers ssDNA gap accumulation and heightened PARP inhibitor sensitivity.Nature communications · 2026Article
- Nuclear IDH3A Drives Transcriptional Programs in Melanoma via the YBX1-JUN/FOS Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cross-Scale Convergence in Epigenetic Gene Regulation: A Perspective on Functional Enrichment Analytics for Cancer.Current issues in molecular biology · 2026Article
- Infection and α-ketoglutarate/oxygen inhibition converge to CDC20 to promote cancer cell aneuploidy.Signal transduction and targeted therapy · 2026Article
- Tuning epigenetics to enhance cancer virotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Metabolites with a message: impacts on epigenetics and implications for epimetabopathies.EMBO reports · 2026Review
- Twisting the End Game: How Telomere Chromatin Modifications Shape Telomere Maintenance.Aging cell · 2026Review
- Loss of the mitochondrial SAM transporter reveals a lipoylation-dependent metabolic vulnerability in the postnatal heart.Science advances · 2026Article
- IDH-Mutant Diffuse Glioma: From Metabolic Origins to Targeted Therapy.Journal of clinical medicine · 2026Review
- 2-Hydroxyglutarate Redirects Fatty Acid Partitioning to Mitigate Lipotoxic Stress and Preserve Metabolic Fuel.bioRxiv : the preprint server for biology · 2026Article
1,682 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as α-KG does in the active site of histone demethylases. Ectopic expression of tumor-derived IDH1 and IDH2 mutants inhibits histone demethylation and 5mC hydroxylation. In glioma, IDH1 mutations are associated with increased histone methylation and decreased 5-hydroxylmethylcytosine (5hmC). Hence, tumor-derived IDH1 and IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.