The DOI matches its Crossref record; 136 of the 138 references it cites were found in a registry or an index.
Metabolism, Activity, and Targeting of D- and L-2-Hydroxyglutarates
Open accessAbstract
Isocitrate dehydrogenases (IDH1/2) are frequently mutated in multiple types of human cancer, resulting in neomorphic enzymes that convert α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG). The current view on the mechanism of IDH mutation holds that 2-HG acts as an antagonist of α-KG to competitively inhibit the activity of α-KG-dependent dioxygenases, including those involved in histone and DNA demethylation. Recent studies have implicated 2-HG in activities beyond epigenetic modification. Multiple enzymes have been discovered that lack mutations but that can nevertheless produce 2-HG promiscuously under hypoxic or acidic conditions. Therapies are being developed to treat IDH-mutant cancers by targeting either the mutant IDH enzymes directly or the pathways sensitized by 2-HG.
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“Remarkably, almost all IDH1/2 mutations occur in a few unique locations in the active site of the enzymes, which results in the acquirement of a neomorphic enzymatic activity converting α-KG to the oncometabolite D-2-HG118-120.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [119]
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An Integrated Genomic Analysis of Human Glioblastoma Multiforme
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IDH1 and IDH2 Mutations in Gliomas
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Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
The Cancer Genome Atlas Research Network (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1301689 · Cited by 5,078
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
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“EGLN/PHD-mediated regulation of HIF-1α is the core of ancient oxygen-monitoring machinery used by metazoans from the nematode Caenorhabditis elegans to humans [129].”
BackgroundComprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas
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Recurring mutations found by sequencing an acute myeloid leukemia genome
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Metadata
- Authors
- Ye, D., Guan, K.-L., & Xiong, Y.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Ye, Dan
- Xiong, Yue
- Venue
- Trends in Cancer
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 4
- Issue
- 2
- Pages
- 151-165
- ISSN
- 2405-8025 (ISSN-L)
- 2405-8033
- PMC
- PMC5884165
- OpenAlex
- W2782192099
- Cited by
- 242
- References
- 138
- Citations by year
- 2026: 26 · 2025: 31 · 2024: 23 · 2023: 28 · 2022: 30 · 2021: 38 · 2020: 29 · 2019: 25 · 2018: 11
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Trends in cancer (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Key R&D Program of China (2016YFA0501800)
- NSFC (81522033, 81372198)
- Shanghai Committee of Science and Technology (16JC1404000)
- NIH (CA196878, GM51586, CA063834, CA163834)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Keywords
- 2-hydroxyglutarate, IDH mutation, IDH1, IDH2, alpha-ketoglutarate, epigenetic demethylation, histone demethylation, DNA demethylation, hypoxia, acidosis
- MeSH terms
- Animals, Glutarates, Humans, Isocitrate Dehydrogenase, Mutation, Neoplasms, Molecular Targeted Therapy
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