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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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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