PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33709779-2 2021 The oral, targeted, mutant IDH1 (mIDH1) inhibitor ivosidenib (AG-120) suppresses production of the oncometabolite D-2-hydroxyglutarate, promoting disease stabilization and improved progression-free survival (PFS) in mIDH1 IHCC. alpha-hydroxyglutarate 114-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-31 33244787-3 2021 The most prominent genetic alterations in diffuse glioma are mutations in the isocitrate dehydrogenase (IDH) genes that generate the immunosuppressive oncometabolite D-2-hydroxyglutarate. alpha-hydroxyglutarate 166-186 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 78-102 33244787-3 2021 The most prominent genetic alterations in diffuse glioma are mutations in the isocitrate dehydrogenase (IDH) genes that generate the immunosuppressive oncometabolite D-2-hydroxyglutarate. alpha-hydroxyglutarate 166-186 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 104-107 33981605-2 2021 Mutations in IDH lead to loss of normal enzymatic activity and gain of neomorphic activity that irreversibly converts alpha-KG to 2-hydroxyglutarate (2-HG), which can competitively inhibit a-KG-dependent enzymes, subsequently induces cell metabolic reprograming, inhibits cell differentiation, and initiates cell tumorigenesis. alpha-hydroxyglutarate 130-148 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-16 33981605-2 2021 Mutations in IDH lead to loss of normal enzymatic activity and gain of neomorphic activity that irreversibly converts alpha-KG to 2-hydroxyglutarate (2-HG), which can competitively inhibit a-KG-dependent enzymes, subsequently induces cell metabolic reprograming, inhibits cell differentiation, and initiates cell tumorigenesis. alpha-hydroxyglutarate 150-154 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-16 33894275-6 2021 Also, in IDH1/2 mutant cancer, NADPH serves as the cofactor to generate D-2 hydroxyglutarate, an oncometabolite. alpha-hydroxyglutarate 72-92 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 9-15 33832922-1 2021 Somatic mutations in hotspot regions of the cytosolic or mitochondrial isoforms of the isocitrate dehydrogenase gene (IDH1 and IDH2, respectively) contribute to the pathogenesis of acute myeloid leukemia (AML) by producing the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 242-260 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 118-122 33832922-1 2021 Somatic mutations in hotspot regions of the cytosolic or mitochondrial isoforms of the isocitrate dehydrogenase gene (IDH1 and IDH2, respectively) contribute to the pathogenesis of acute myeloid leukemia (AML) by producing the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 262-266 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 118-122 33360716-2 2021 IDH mutations cause neomorphic enzymatic activity that results in the production of the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 103-121 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 33360716-2 2021 IDH mutations cause neomorphic enzymatic activity that results in the production of the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 123-127 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 33668509-1 2021 Approximately 80% of low-grade glioma (LGGs) harbor mutant isocitrate dehydrogenase 1/2 (IDH1/2) driver mutations leading to accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 160-178 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 89-95 33668509-1 2021 Approximately 80% of low-grade glioma (LGGs) harbor mutant isocitrate dehydrogenase 1/2 (IDH1/2) driver mutations leading to accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 180-184 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 89-95 33523209-8 2021 RESULTS: Assessment of IDH mutation status using DESI-MS/MS to measure 2-hydroxyglutarate (2-HG) ion intensities from tumor cores yielded a sensitivity, specificity, and overall diagnostic accuracy of 89, 100, and 94%, respectively (ncore = 71). alpha-hydroxyglutarate 71-89 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-26 33523209-8 2021 RESULTS: Assessment of IDH mutation status using DESI-MS/MS to measure 2-hydroxyglutarate (2-HG) ion intensities from tumor cores yielded a sensitivity, specificity, and overall diagnostic accuracy of 89, 100, and 94%, respectively (ncore = 71). alpha-hydroxyglutarate 91-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-26 32940938-15 2021 Among 2-HG ratios, the highest AUC for the identification of IDH mutant status was achieved using the 2-HG/NAA (AUC = 0.8, 95% CI 0.67-.89). alpha-hydroxyglutarate 6-10 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 61-64 33043739-1 2021 Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in Myeloid Neoplams (MNs) exhibit DNA hypermethylation via 2-hydroxyglutarate (2HG) over-production. alpha-hydroxyglutarate 116-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 33632416-12 2021 One of the major contributions of magnetic resonance to the assessment of brain tumors has been the non-invasive determination of 2-hydroxyglutarate (2HG) in tumors harboring a mutation in isocitrate dehydrogenase 1 (IDH1). alpha-hydroxyglutarate 130-148 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 189-215 33632416-12 2021 One of the major contributions of magnetic resonance to the assessment of brain tumors has been the non-invasive determination of 2-hydroxyglutarate (2HG) in tumors harboring a mutation in isocitrate dehydrogenase 1 (IDH1). alpha-hydroxyglutarate 130-148 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 217-221 33266275-1 2020 Mutations in the isocitrate dehydrogenase (IDH1 or IDH2) genes are common in enchondromas and chondrosarcomas, and lead to elevated levels of the oncometabolite D-2-hydroxyglutarate causing widespread changes in the epigenetic landscape of these tumors. alpha-hydroxyglutarate 161-181 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 43-47 33212941-3 2020 To avoid tumor biopsy, dedicated spectroscopic techniques have been proposed to detect D-2-hydroxyglutarate (2-HG), the main metabolite of IDH, directly in vivo. alpha-hydroxyglutarate 87-107 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 139-142 33212941-3 2020 To avoid tumor biopsy, dedicated spectroscopic techniques have been proposed to detect D-2-hydroxyglutarate (2-HG), the main metabolite of IDH, directly in vivo. alpha-hydroxyglutarate 109-113 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 139-142 31847543-8 2020 However, even wild-type IDH1 and IDH2, notably under shifts toward reductive carboxylation glutaminolysis or changes in other enzymes, lead to "intermediate" 0.01-0.1 mM 2HG levels, e.g. in breast carcinoma, compared to 10-8 M in non-cancer cells. alpha-hydroxyglutarate 170-173 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-28 32853017-4 2020 The objective of this study was to confirm or to reject the hypothesis of the direct correlation of 2-HG concentration in tumor tissue and the results from IDH 1/IDH 2 point mutation analyses. alpha-hydroxyglutarate 100-104 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 156-161 33019704-1 2020 Acute myeloid leukemia (AML) frequently harbors mutations in isocitrate 1 (IDH1) and 2 (IDH2) genes, leading to the formation of the oncometabolite (2R)-hydroxyglutaric acid (2R-HG) with epigenetic consequences for AML proliferation and differentiation. alpha-hydroxyglutarate 148-173 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 75-79 32727816-2 2020 Mutant IDH1 favours the production of 2-hydroxyglutarate, an oncometabolite with multiple downstream effects which promote tumourigenesis. alpha-hydroxyglutarate 38-56 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 32622311-3 2020 Because IDH1R132H requires a wild-type allele to produce (D)-2-hydroxyglutarate for epigenetic reprogramming, loss of IDH1R132H heterozygosity is associated with glioma progression in an IDH1-wildtype-like phenotype. alpha-hydroxyglutarate 57-79 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 8-12 32929121-5 2020 Clinical translation of AC/DC and MRSI is demonstrated in a patient with mutant-IDH1 glioma where it enables imaging of D-2-hydroxyglutarate oncometabolite with a 2.8-fold increase in contrast-to-noise ratio at higher resolution and more brain coverage compared to previous 7 T studies. alpha-hydroxyglutarate 120-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 80-84 32878781-2 2020 IDH1 mutants produce 2-hydroxyglutarate (2-HG), an oncometabolite, from alpha-ketoglutarate (alpha-KG). alpha-hydroxyglutarate 21-39 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 32878781-2 2020 IDH1 mutants produce 2-hydroxyglutarate (2-HG), an oncometabolite, from alpha-ketoglutarate (alpha-KG). alpha-hydroxyglutarate 41-45 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 32878781-8 2020 In addition, KRC-09 decreased the concentration of intracellular 2-HG in the U-87 MG cell line harboring IDH1 R132H. alpha-hydroxyglutarate 65-69 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 105-109 32003035-0 2020 In vivo MRS measurement of 2-hydroxyglutarate in patient-derived IDH-mutant xenograft mouse models versus glioma patients. alpha-hydroxyglutarate 27-45 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 65-68 32705169-2 2020 Dysregulated expression of wild-type isocitrate dehydrogenase 1 (IDH1) has been demonstrated to promote the progression of primary GBM without accumulating D-2-hydroxyglutarate, which differs from IDH1 mutation-related mechanisms of tumorigenesis. alpha-hydroxyglutarate 156-176 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 65-69 32825279-2 2020 IDH mutants confer a neomorphic enzyme activity that converts alpha-ketoglutarate to an oncometabolite D-2-hydroxyglutarate, which impacts cellular epigenetics and metabolism. alpha-hydroxyglutarate 103-123 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 32824685-4 2020 Indeed, some IDH1 point mutations induce widespread epigenetic alterations by means of a gain-of-function of the enzyme, which becomes able to produce the oncometabolite 2-hydroxyglutarate, with inhibitory activity on alpha-ketoglutarate-dependent enzymes, such as DNA and histone demethylases. alpha-hydroxyglutarate 170-188 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 32777735-3 2020 Cancer-associated substitutions in IDH1 and IDH2 impair wild-type production of 2-oxoglutarate and reduced nicotinamide adenine dinucleotide phosphate (NADPH) from isocitrate and oxidised nicotinamide adenine dinucleotide phosphate (NADP+ ), and substantially promote the IDH variant catalysed conversion of 2-oxoglutarate to d-2-hydroxyglutarate (d-2HG). alpha-hydroxyglutarate 326-346 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 32777735-3 2020 Cancer-associated substitutions in IDH1 and IDH2 impair wild-type production of 2-oxoglutarate and reduced nicotinamide adenine dinucleotide phosphate (NADPH) from isocitrate and oxidised nicotinamide adenine dinucleotide phosphate (NADP+ ), and substantially promote the IDH variant catalysed conversion of 2-oxoglutarate to d-2-hydroxyglutarate (d-2HG). alpha-hydroxyglutarate 326-346 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-38 32777735-3 2020 Cancer-associated substitutions in IDH1 and IDH2 impair wild-type production of 2-oxoglutarate and reduced nicotinamide adenine dinucleotide phosphate (NADPH) from isocitrate and oxidised nicotinamide adenine dinucleotide phosphate (NADP+ ), and substantially promote the IDH variant catalysed conversion of 2-oxoglutarate to d-2-hydroxyglutarate (d-2HG). alpha-hydroxyglutarate 348-353 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 32777735-3 2020 Cancer-associated substitutions in IDH1 and IDH2 impair wild-type production of 2-oxoglutarate and reduced nicotinamide adenine dinucleotide phosphate (NADPH) from isocitrate and oxidised nicotinamide adenine dinucleotide phosphate (NADP+ ), and substantially promote the IDH variant catalysed conversion of 2-oxoglutarate to d-2-hydroxyglutarate (d-2HG). alpha-hydroxyglutarate 348-353 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-38 32754276-2 2020 IDH1mut catalyzes the reduction of alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG), an oncometabolite which drives tumorigenesis. alpha-hydroxyglutarate 69-87 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 32754276-2 2020 IDH1mut catalyzes the reduction of alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG), an oncometabolite which drives tumorigenesis. alpha-hydroxyglutarate 89-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 32576825-6 2020 Further we verify that D-2-hydroxyglutarate (D-2HG) is high in venous plasma from patients with isocitrate dehydrogenases1 (IDH1) mutations. alpha-hydroxyglutarate 23-43 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 124-128 32576825-6 2020 Further we verify that D-2-hydroxyglutarate (D-2HG) is high in venous plasma from patients with isocitrate dehydrogenases1 (IDH1) mutations. alpha-hydroxyglutarate 45-50 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 124-128 32494005-2 2020 Increased levels of the metabolites 2-hydroxyglutarate, succinate and fumarate occur in human malignancies owing to somatic mutations in the isocitrate dehydrogenase-1 or -2 (IDH1 or IDH2) genes, or germline mutations in the fumarate hydratase (FH) and succinate dehydrogenase genes (SDHA, SDHB, SDHC and SDHD), respectively2-4. alpha-hydroxyglutarate 36-54 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 175-179 32208957-2 2020 Mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) enzymes occur in up to 65% of chondrosarcomas, resulting in accumulation of the oncometabolite D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 150-170 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-53 32208957-2 2020 Mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) enzymes occur in up to 65% of chondrosarcomas, resulting in accumulation of the oncometabolite D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 172-176 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-53 32380538-1 2020 Isocitrate dehydrogenase (IDH) 1 and 2 mutations result in overproduction of D-2-hydroxyglutarate (2-HG) and impaired cellular differentiation. alpha-hydroxyglutarate 77-97 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-38 32380538-1 2020 Isocitrate dehydrogenase (IDH) 1 and 2 mutations result in overproduction of D-2-hydroxyglutarate (2-HG) and impaired cellular differentiation. alpha-hydroxyglutarate 99-103 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-38 32380538-5 2020 Multiple mechanisms contributed to acquired resistance, particularly outgrowth of RTK pathway mutations and 2-HG-restoring mutations (second-site IDH1 mutations, IDH2 mutations). alpha-hydroxyglutarate 108-112 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 146-150 32296873-1 2020 PURPOSE: Isocitrate dehydrogenase (IDH) mutations lead to formation of the oncometabolite 2-hydroxyglutarate (2-HG), which is elevated in several solid and liquid tumors. alpha-hydroxyglutarate 90-108 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 9-33 32296873-1 2020 PURPOSE: Isocitrate dehydrogenase (IDH) mutations lead to formation of the oncometabolite 2-hydroxyglutarate (2-HG), which is elevated in several solid and liquid tumors. alpha-hydroxyglutarate 90-108 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-38 32296873-1 2020 PURPOSE: Isocitrate dehydrogenase (IDH) mutations lead to formation of the oncometabolite 2-hydroxyglutarate (2-HG), which is elevated in several solid and liquid tumors. alpha-hydroxyglutarate 110-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 9-33 32296873-1 2020 PURPOSE: Isocitrate dehydrogenase (IDH) mutations lead to formation of the oncometabolite 2-hydroxyglutarate (2-HG), which is elevated in several solid and liquid tumors. alpha-hydroxyglutarate 110-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-38 31609487-2 2020 Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations have been recently described in low-grade cartilaginous neoplasms which lead to increased D-2-hydroxyglutarate (2HG) oncometabolite production, promoting tumorigenesis. alpha-hydroxyglutarate 143-163 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 31609487-2 2020 Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations have been recently described in low-grade cartilaginous neoplasms which lead to increased D-2-hydroxyglutarate (2HG) oncometabolite production, promoting tumorigenesis. alpha-hydroxyglutarate 143-163 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 31609487-2 2020 Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations have been recently described in low-grade cartilaginous neoplasms which lead to increased D-2-hydroxyglutarate (2HG) oncometabolite production, promoting tumorigenesis. alpha-hydroxyglutarate 165-168 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 31609487-2 2020 Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations have been recently described in low-grade cartilaginous neoplasms which lead to increased D-2-hydroxyglutarate (2HG) oncometabolite production, promoting tumorigenesis. alpha-hydroxyglutarate 165-168 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 31609487-6 2020 6/14 IDH-mutated DDCHS showed elevated 2HG in tumor relative to matched normal tissue. alpha-hydroxyglutarate 39-42 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 5-8 31609487-9 2020 Similar to other IDH-mutated tumor types, IDH-mutated DDCHS also show elevated 2HG level, indicating that the oncometabolite activity of 2HG may contribute to DDCHS oncogenesis and progression. alpha-hydroxyglutarate 79-82 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-45 31609487-9 2020 Similar to other IDH-mutated tumor types, IDH-mutated DDCHS also show elevated 2HG level, indicating that the oncometabolite activity of 2HG may contribute to DDCHS oncogenesis and progression. alpha-hydroxyglutarate 137-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 17-20 31609487-9 2020 Similar to other IDH-mutated tumor types, IDH-mutated DDCHS also show elevated 2HG level, indicating that the oncometabolite activity of 2HG may contribute to DDCHS oncogenesis and progression. alpha-hydroxyglutarate 137-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-45 31028664-1 2020 Background Mutant isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) enzymes produce the oncometabolite D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 98-118 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 52-56 31895700-5 2020 The phenomenon was not observed with other IDH1/2 inhibitors and occurred in IDH2-deficient CRISPR-engineered progenitors independently of D-2-hydroxyglutarate. alpha-hydroxyglutarate 139-159 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 43-49 31983428-1 2020 Isocitrate dehydrogenase (IDH) mutations are found in low-grade gliomas, and the product of the IDH mutant (MT), 2-hydroxyglutarate (2-HG), is the first known oncometabolite. alpha-hydroxyglutarate 113-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 96-99 31983428-1 2020 Isocitrate dehydrogenase (IDH) mutations are found in low-grade gliomas, and the product of the IDH mutant (MT), 2-hydroxyglutarate (2-HG), is the first known oncometabolite. alpha-hydroxyglutarate 133-137 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 96-99 31505989-1 2020 Mutations in the enzyme isocitrate dehydrogenase 1 (IDH1) lead to metabolic alterations and a sustained formation of 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 117-135 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-50 31505989-1 2020 Mutations in the enzyme isocitrate dehydrogenase 1 (IDH1) lead to metabolic alterations and a sustained formation of 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 117-135 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 52-56 31909698-1 2020 Background Isocitrate dehydrogenase (IDH) mutations are highly frequent in glioma, producing high levels of the oncometabolite D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 149-154 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 11-35 31909698-1 2020 Background Isocitrate dehydrogenase (IDH) mutations are highly frequent in glioma, producing high levels of the oncometabolite D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 149-154 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 37-40 31909698-2 2020 Hence, D-2HG represents a valuable imaging marker for IDH-mutated human glioma. alpha-hydroxyglutarate 7-12 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 54-57 31909698-3 2020 Purpose To develop and evaluate a super-resolution three-dimensional (3D) MR spectroscopic imaging strategy to map D-2HG and tumor metabolism in IDH-mutated human glioma. alpha-hydroxyglutarate 115-120 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 145-148 32111066-4 2020 Similarly, lowering NADPH by mutant isocitrate dehydrogenase 1/2 (IDH1/2) which produces D-2-hydroxyglutarate (D-2HG), an oncometabolite that downregulates nicotinate phosphoribosyltransferase (NAPRT) via hypermethylation on the promoter region, results in epigenetic regulation. alpha-hydroxyglutarate 89-109 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-72 31841594-1 2020 Ivosidenib (AG-120) is an oral, targeted agent that suppresses production of the oncometabolite 2-hydroxyglutarate via inhibition of the mutant isocitrate dehydrogenase 1 (IDH1; mIDH1) enzyme. alpha-hydroxyglutarate 96-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 144-170 31841594-1 2020 Ivosidenib (AG-120) is an oral, targeted agent that suppresses production of the oncometabolite 2-hydroxyglutarate via inhibition of the mutant isocitrate dehydrogenase 1 (IDH1; mIDH1) enzyme. alpha-hydroxyglutarate 96-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 172-176 31586149-2 2020 Mutant IDH produces R-2-hydroxyglutarate (R-2HG), which induces histone- and DNA-hypermethylation through the inhibition of epigenetic regulators, thus linking metabolism to tumorigenesis. alpha-hydroxyglutarate 20-40 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 31586149-4 2020 Treatment of IDH1mut primary AML cells reduced 2-hydroxyglutarate levels (2HG) and induced myeloid differentiation in vitro. alpha-hydroxyglutarate 47-65 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-20 31727689-6 2020 Mutant IDH catalyzes the conversion of alpha-ketoglutarate (alpha-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), which induces aberrant epigenetic status and contributes to malignant progression, and is therefore a potential therapeutic target for IDH mutant tumors. alpha-hydroxyglutarate 92-110 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 31727689-6 2020 Mutant IDH catalyzes the conversion of alpha-ketoglutarate (alpha-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), which induces aberrant epigenetic status and contributes to malignant progression, and is therefore a potential therapeutic target for IDH mutant tumors. alpha-hydroxyglutarate 92-110 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 254-257 31727689-6 2020 Mutant IDH catalyzes the conversion of alpha-ketoglutarate (alpha-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), which induces aberrant epigenetic status and contributes to malignant progression, and is therefore a potential therapeutic target for IDH mutant tumors. alpha-hydroxyglutarate 112-116 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 31727689-6 2020 Mutant IDH catalyzes the conversion of alpha-ketoglutarate (alpha-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), which induces aberrant epigenetic status and contributes to malignant progression, and is therefore a potential therapeutic target for IDH mutant tumors. alpha-hydroxyglutarate 112-116 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 254-257 31650436-1 2020 Isocitrate dehydrogenase 1/2 (IDH1/2) mutations are often detected in lower-grade gliomas (LGG) and result into 2-hydroxyglutarate (2HG) synthesis. alpha-hydroxyglutarate 112-130 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-36 31935911-5 2020 IDH mutations and D-2HG are thought to contribute to tumorigenesis due to the role of D-2HG as a competitive inhibitor of alpha-KG-dependent dioxygenases. alpha-hydroxyglutarate 86-91 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 31935911-8 2020 We observed that D-2HG production, anchorage-independent growth, and cell migration were significantly suppressed in the IDH1mut knockout cells. alpha-hydroxyglutarate 17-22 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 121-125 31935911-9 2020 Loss of IDH1mut also led to a marked attenuation of chondrosarcoma formation and D-2HG production in a xenograft model. alpha-hydroxyglutarate 81-86 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 8-15 31485826-2 2020 IDH enzyme normally catalyzes isocitrate to alpha-keto-glutarate (alpha-KG), but once the gene is mutated it produces an "oncometabolite", 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 139-157 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 32055803-2 2020 Somatic point mutations in IDH1/2 that are found in rare distinct subsets of cancers confer a gain of function in cancer cells which results in the accumulation and secretion in vast excess of the oncometabolite D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 212-232 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-31 32055803-2 2020 Somatic point mutations in IDH1/2 that are found in rare distinct subsets of cancers confer a gain of function in cancer cells which results in the accumulation and secretion in vast excess of the oncometabolite D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 234-239 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-31 32055803-5 2020 In addition, D-2HG is a biomarker suitable for the detection of IDH1/2 mutations at diagnosis, and is also predictive of clinical response. alpha-hydroxyglutarate 13-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 64-70 31893370-8 2020 Specifically, we describe the generation of reporter cell lines that express epitope-tagged R132H-IDH1 or R172K-IDH2 and produce (D)2-hydroxyglutarate in a doxycycline-dependent manner. alpha-hydroxyglutarate 129-150 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 98-102 31929772-3 2020 For example, D-2-hydroxyglutarate, generated due to the activity of mutated mitochondrial isocitrate dehydrogenase (IDH), has been implicated in the pathogenesis of leukemia. alpha-hydroxyglutarate 13-33 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 116-119 31526886-5 2020 The oncometabolite 2-hydroxyglutarate (2HG), accumulated in gliomas IDH-mutant, can be detected in vivo by means of magnetic resonance spectroscopy (MRS). alpha-hydroxyglutarate 19-37 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 68-71 31853670-5 2019 The identification of 2-hydroxyglutarate by MR spectroscopy can reflect the IDH status of the tumor. alpha-hydroxyglutarate 22-40 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 76-79 31888244-2 2019 IDH1wt converts isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+), whereas IDH1R132H uses alpha-ketoglutarate and NADPH to generate the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 202-220 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 31888244-2 2019 IDH1wt converts isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+), whereas IDH1R132H uses alpha-ketoglutarate and NADPH to generate the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 222-226 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 31810230-1 2019 Chondrosarcomas are chemo- and radiotherapy resistant and frequently harbor mutations in isocitrate dehydrogenase (IDH1 or IDH2), causing increased levels of D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 158-178 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 115-119 31810230-1 2019 Chondrosarcomas are chemo- and radiotherapy resistant and frequently harbor mutations in isocitrate dehydrogenase (IDH1 or IDH2), causing increased levels of D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 180-186 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 115-119 31768950-2 2019 Mutant IDH reveals an altered enzymatic activity leading to the synthesis of 2-hydroxyglutarate, which has been implicated in epigenetic mechanisms of oncogenesis. alpha-hydroxyglutarate 77-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 31577603-3 2019 IDH-mutant tumors produce the "onco-metabolite", 2-hydroxyglutarate. alpha-hydroxyglutarate 49-67 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 31795195-9 2019 Plasma metabolite analysis revealed biomarker metabolites associated with ICC and in particular 2-hydroxyglutarate (2-HG) levels were elevated in both samples from the only patient showing a variant allele in IDH1. alpha-hydroxyglutarate 96-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 209-213 31795195-9 2019 Plasma metabolite analysis revealed biomarker metabolites associated with ICC and in particular 2-hydroxyglutarate (2-HG) levels were elevated in both samples from the only patient showing a variant allele in IDH1. alpha-hydroxyglutarate 116-120 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 209-213 31504231-3 2019 The rapid biomedical advancement has been driven primarily by the realization of a neomorphic activity of IDH1 mutation that produces high levels of (d)-2-hydroxyglutarate, a metabolite believed to promote glioma initiation and progression through epigenetic and metabolic reprogramming. alpha-hydroxyglutarate 149-171 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 106-110 31983120-1 2019 PURPOSE: To investigate whether IDH1 mutation or 2-hydroxyglutarate (2-HG), the oncometabolite produced by IDH mutations, is correlated to epithelial-mesenchymal transition (EMT)-like phenotype in glioma cells, so as to clarify how IDH1 mutation is good prognostic factor while 2-HG, being its oncometabolite, remains unknown. alpha-hydroxyglutarate 278-282 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-35 31652645-3 2019 Mutant IDH generates high levels of 2-hydroxyglutarate (2-HG) that inhibit various components of the epigenetic machinery, including histone and DNA demethylases. alpha-hydroxyglutarate 36-54 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 31652645-3 2019 Mutant IDH generates high levels of 2-hydroxyglutarate (2-HG) that inhibit various components of the epigenetic machinery, including histone and DNA demethylases. alpha-hydroxyglutarate 56-60 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 31591388-0 2019 The oncometabolite 2-hydroxyglutarate produced by mutant IDH1 sensitizes cells to ferroptosis. alpha-hydroxyglutarate 19-37 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 57-61 31591388-4 2019 Deletion of the mutant IDH1 allele in IDH1 heterozygous tumor cells or pharmacological inhibition of mutant IDH1 to produce the oncometabolite D-2-hydroxyglutarate (D-2-HG) confers resistance to erastin-induced ferroptosis. alpha-hydroxyglutarate 143-163 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-27 31591388-4 2019 Deletion of the mutant IDH1 allele in IDH1 heterozygous tumor cells or pharmacological inhibition of mutant IDH1 to produce the oncometabolite D-2-hydroxyglutarate (D-2-HG) confers resistance to erastin-induced ferroptosis. alpha-hydroxyglutarate 165-171 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-27 31292202-2 2019 IDH1/2 active site mutations confer a neomorphic enzyme activity producing the oncometabolite D-2-hydroxyglutarate (D-2HG), which generates the glioma CpG island methylation phenotype (G-CIMP). alpha-hydroxyglutarate 94-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 31292202-2 2019 IDH1/2 active site mutations confer a neomorphic enzyme activity producing the oncometabolite D-2-hydroxyglutarate (D-2HG), which generates the glioma CpG island methylation phenotype (G-CIMP). alpha-hydroxyglutarate 116-121 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 31406254-4 2019 Isocitrate dehydrogenase (IDH) mutations, which are detected in ~50% of chondrosarcoma patients, contribute to malignant transformation by catalyzing the production of 2-hydroxyglutarate (2-HG), a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. alpha-hydroxyglutarate 168-186 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 31406254-4 2019 Isocitrate dehydrogenase (IDH) mutations, which are detected in ~50% of chondrosarcoma patients, contribute to malignant transformation by catalyzing the production of 2-hydroxyglutarate (2-HG), a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. alpha-hydroxyglutarate 168-186 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 31406254-4 2019 Isocitrate dehydrogenase (IDH) mutations, which are detected in ~50% of chondrosarcoma patients, contribute to malignant transformation by catalyzing the production of 2-hydroxyglutarate (2-HG), a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. alpha-hydroxyglutarate 188-192 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 31406254-4 2019 Isocitrate dehydrogenase (IDH) mutations, which are detected in ~50% of chondrosarcoma patients, contribute to malignant transformation by catalyzing the production of 2-hydroxyglutarate (2-HG), a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. alpha-hydroxyglutarate 188-192 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 31632056-2 2019 A variety of mutations have been identified at the molecular level, such as those in the IDH1/2 gene, which causes a gain of function of the isocitrate dehydrogenase enzyme, generating high levels of the (R)-2-hydroxyglutarate oncometabolite, which competitively inhibits dioxygenase enzymes. alpha-hydroxyglutarate 204-226 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 89-95 31475115-9 2019 Gain-of-function mutations in IDH1, such as c.394C>T/p.Arg132Cys, create a neo-activity of isocitrate dehydrogenase 1 converting alpha-ketoglutarate into the oncometabolite D-2-hydroxyglutarate, inhibiting alpha-ketoglutarate-dependent enzymes, such as histone and DNA demethylases. alpha-hydroxyglutarate 176-196 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 31211872-0 2019 Abundance of d-2-hydroxyglutarate in G2/M is determined by FOXM1 in mutant IDH1-expressing cells. alpha-hydroxyglutarate 13-33 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 75-79 31257503-3 2019 IDH1 and 2 mutations result in the loss of normal catalytic function and acquire neomorphic activity, facilitating the conversion of alpha-KG into an oncometabolite, (R)-2-hydroxyglutarate, which can cause epigenetic modifications and tumorigenesis. alpha-hydroxyglutarate 166-188 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-10 31278288-4 2019 In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. alpha-hydroxyglutarate 61-81 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 36-40 31278288-4 2019 In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. alpha-hydroxyglutarate 61-81 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 36-39 31155409-1 2019 BACKGROUND: Mutations in isocitrate dehydrogenase (IDH)1/2 genes result in nicotinamide adenine dinucleotide phosphate-dependent reduction of alpha-ketoglutarate and formation of 2-hydroxyglutarate, which blocks normal cellular differentiation and promotes leukemogenesis. alpha-hydroxyglutarate 179-197 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 51-56 31182575-1 2019 Oncogenic IDH1/2 mutations produce 2-hydroxyglutarate (2HG), resulting in competitive inhibition of DNA and protein demethylation. alpha-hydroxyglutarate 35-53 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-16 31221981-5 2019 Furthermore, gain-of-function mutations in genes encoding metabolic enzymes, such as isocitrate dehydrogenases (IDH)1/2, drive tumor progression by producing an oncometabolite, D-2-hydroxyglutarate (D-2HG), which is a competitive inhibitor of alpha-ketoglutarate, O2-dependent dioxygenases such as Jumonji domain-containing histone demethylases, and DNA demethylases. alpha-hydroxyglutarate 177-197 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 85-119 31221981-5 2019 Furthermore, gain-of-function mutations in genes encoding metabolic enzymes, such as isocitrate dehydrogenases (IDH)1/2, drive tumor progression by producing an oncometabolite, D-2-hydroxyglutarate (D-2HG), which is a competitive inhibitor of alpha-ketoglutarate, O2-dependent dioxygenases such as Jumonji domain-containing histone demethylases, and DNA demethylases. alpha-hydroxyglutarate 199-204 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 85-119 31263678-3 2019 First, IDH mutations can produce high levels of 2-hydroxyglutaric acid (2-HG), thereby inhibiting glioma stem cell differentiation. alpha-hydroxyglutarate 48-70 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 31263678-3 2019 First, IDH mutations can produce high levels of 2-hydroxyglutaric acid (2-HG), thereby inhibiting glioma stem cell differentiation. alpha-hydroxyglutarate 72-76 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 30777876-0 2019 Tissue 2-Hydroxyglutarate as a Biomarker for Isocitrate Dehydrogenase Mutations in Gliomas. alpha-hydroxyglutarate 7-25 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 45-69 30777876-2 2019 IDH mutations lead to preferential accumulation of the R- relative to the S-enantiomer of 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 90-108 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 30990380-0 2019 False-Positive Measurement at 2-Hydroxyglutarate MR Spectroscopy in Isocitrate Dehydrogenase Wild-Type Glioblastoma: A Multifactorial Analysis. alpha-hydroxyglutarate 30-48 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 68-92 30990380-15 2019 Conclusion Necrosis and apparent diffusion coefficient were associated with false-positive measurements of 2-hydroxyglutarate at MR spectroscopy in patients with isocitrate dehydrogenase wild-type glioblastoma. alpha-hydroxyglutarate 107-125 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 162-186 31139406-1 2019 Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D-2-hydroxyglutarate (D-2-HG) at the expense of alpha-ketoglutarate (alpha-KG) and NADPH. alpha-hydroxyglutarate 190-210 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 25-51 31139406-1 2019 Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D-2-hydroxyglutarate (D-2-HG) at the expense of alpha-ketoglutarate (alpha-KG) and NADPH. alpha-hydroxyglutarate 190-210 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 53-57 31139406-1 2019 Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D-2-hydroxyglutarate (D-2-HG) at the expense of alpha-ketoglutarate (alpha-KG) and NADPH. alpha-hydroxyglutarate 212-218 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 25-51 31139406-1 2019 Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D-2-hydroxyglutarate (D-2-HG) at the expense of alpha-ketoglutarate (alpha-KG) and NADPH. alpha-hydroxyglutarate 212-218 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 53-57 31139406-7 2019 Preventing glutamate processing in HCT116-IDH1 wt/R132H cells with EGCG resulted in reduction of D-2-HG production. alpha-hydroxyglutarate 99-103 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-46 31165048-2 2019 The neomorphic mutation in IDH generates an oncometabolite product, 2-hydroxyglutarate (2HG), which has been linked to the disruption of metabolic and epigenetic mechanisms responsible for cellular differentiation and is likely an early and critical contributor to oncogenesis. alpha-hydroxyglutarate 68-86 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-30 31092874-9 2019 Further, incubation of IDH wild type cells for up to 48 hours with 5 mM D-2-HG did not result in a significant increase in either D2HDH protein abundance or enzyme activity. alpha-hydroxyglutarate 72-78 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-26 30573870-3 2019 IDH mutation has a remarkable neomorphic activity of converting alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG), which is now commonly referred to as an oncometabolite and biomarker for gliomas. alpha-hydroxyglutarate 98-116 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 30710208-1 2019 Isocitrate dehydrogenase (IDH) I and II mutations in gliomas cause an abnormal accumulation of 2-hydroxyglutarate (2-HG) in these tumor cells. alpha-hydroxyglutarate 95-113 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 30956952-0 2019 (R)-2-hydroxyglutarate drives immune quiescence in the tumor microenvironment of IDH-mutant gliomas. alpha-hydroxyglutarate 0-22 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 81-84 30791611-2 2019 Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. alpha-hydroxyglutarate 118-136 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 45-51 30791611-10 2019 IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.48 +- 1.01vs.0.72 +- 0.38, Pc < 0.001) and myo-Inositol/tCho (2.70 +- 0.90 vs. 1.46 +- 0.51, Pc = 0.011) compared to IDH1 mutation gliomas. alpha-hydroxyglutarate 43-47 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 233-237 30422308-1 2019 BACKGROUND: Acute myeloid leukemia (AML) cells harboring mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) produce the oncometabolite 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 169-187 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 98-102 30422308-9 2019 IDH1/2-mutated patients had significantly higher 2HG levels in serum, urine, bone marrow aspirates, and aspirate cell pellets than wild-type patients. alpha-hydroxyglutarate 49-52 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 30600148-3 2019 Evaluation of the biological activities and function at cellular level showed that compounds 7h, 7i and 7k could effectively suppress the production of 2-hydroxyglutaric acid in U87MG cells expressing IDH1/R132H. alpha-hydroxyglutarate 152-174 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 201-205 30483760-1 2019 The mutation of isocitrate dehydrogenase (IDH)1 (R132H) and IDH2 (R172K) and the induction of hypoxia in various solid tumors results in alterations in metabolic profiles, including the production of the d- or l-forms of 2-hydroxyglutarate (2HG) from alpha-ketoglutarate in aerobic metabolism in the tricarboxylic acid (TCA) cycle. alpha-hydroxyglutarate 221-239 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-47 30611146-3 2019 Assessment of the IDH mutation is key for accurate glioma diagnosis, particularly for differentiating diffuse glioma from other neoplastic and reactive inflammatory conditions, a challenge for the standard intraoperative diagnostic consultation that relies solely on morphology.METHODSBanked glioma specimens (n = 37) were analyzed by desorption electrospray ionization-MS (DESI-MS) to develop a diagnostic method to detect the known altered oncometabolite in IDH-mutant gliomas, 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 480-498 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 18-21 30755816-2 2019 Cells with IDH mutations reduce alphakg to 2-hydroxyglutarate (2HG), an oncometabolite, and 2HG directly transforms normal cells to malignant cells through histone demethylation and epigenetic dysregulation. alpha-hydroxyglutarate 43-61 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 11-14 30470401-3 2019 Mutant IDH produces the oncometabolite 2-hydroxyglutarate, which inhibits enzymes that demethylate genomic DNA and histones. alpha-hydroxyglutarate 39-57 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 30457203-0 2019 Fitting algorithms and baseline correction influence the results of non-invasive in vivo quantitation of 2-hydroxyglutarate with 1 H-MRS. 1 H-MRS enables non-invasive detection of 2-hydroxyglutarate (2-HG), an oncometabolite accumulating in gliomas carrying mutations in the isocitrate dehydrogenase (IDH) genes. alpha-hydroxyglutarate 105-123 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 275-299 30457203-0 2019 Fitting algorithms and baseline correction influence the results of non-invasive in vivo quantitation of 2-hydroxyglutarate with 1 H-MRS. 1 H-MRS enables non-invasive detection of 2-hydroxyglutarate (2-HG), an oncometabolite accumulating in gliomas carrying mutations in the isocitrate dehydrogenase (IDH) genes. alpha-hydroxyglutarate 105-123 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 301-304 30457203-0 2019 Fitting algorithms and baseline correction influence the results of non-invasive in vivo quantitation of 2-hydroxyglutarate with 1 H-MRS. 1 H-MRS enables non-invasive detection of 2-hydroxyglutarate (2-HG), an oncometabolite accumulating in gliomas carrying mutations in the isocitrate dehydrogenase (IDH) genes. alpha-hydroxyglutarate 180-198 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 275-299 30457203-0 2019 Fitting algorithms and baseline correction influence the results of non-invasive in vivo quantitation of 2-hydroxyglutarate with 1 H-MRS. 1 H-MRS enables non-invasive detection of 2-hydroxyglutarate (2-HG), an oncometabolite accumulating in gliomas carrying mutations in the isocitrate dehydrogenase (IDH) genes. alpha-hydroxyglutarate 180-198 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 301-304 30381394-1 2018 Monoallelic point mutations in the gene encoding the cytosolic, NADP+-dependent enzyme isocitrate dehydrogenase 1 (IDH1) cause increased production of the oncometabolite 2-hydroxyglutarate (2-HG) in multiple cancers. alpha-hydroxyglutarate 170-188 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 87-113 30381394-1 2018 Monoallelic point mutations in the gene encoding the cytosolic, NADP+-dependent enzyme isocitrate dehydrogenase 1 (IDH1) cause increased production of the oncometabolite 2-hydroxyglutarate (2-HG) in multiple cancers. alpha-hydroxyglutarate 170-188 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 115-119 30381394-1 2018 Monoallelic point mutations in the gene encoding the cytosolic, NADP+-dependent enzyme isocitrate dehydrogenase 1 (IDH1) cause increased production of the oncometabolite 2-hydroxyglutarate (2-HG) in multiple cancers. alpha-hydroxyglutarate 190-194 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 87-113 30381394-1 2018 Monoallelic point mutations in the gene encoding the cytosolic, NADP+-dependent enzyme isocitrate dehydrogenase 1 (IDH1) cause increased production of the oncometabolite 2-hydroxyglutarate (2-HG) in multiple cancers. alpha-hydroxyglutarate 190-194 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 115-119 30355724-1 2018 Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (IDH1 or IDH2, respectively) contribute to oncogenesis via production of the metabolite 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 173-191 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 86-90 30355724-2 2018 Isoform-selective IDH inhibitors suppress 2HG production and induce clinical responses in patients with IDH1- and IDH2-mutant malignancies. alpha-hydroxyglutarate 42-45 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 18-21 30355724-5 2018 SIGNIFICANCE: IDH-mutant cancers can develop resistance to isoform-selective IDH inhibition by "isoform switching" from mutant IDH1 to mutant IDH2 or vice versa, thereby restoring 2HG production by the tumor. alpha-hydroxyglutarate 180-183 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-17 30355724-5 2018 SIGNIFICANCE: IDH-mutant cancers can develop resistance to isoform-selective IDH inhibition by "isoform switching" from mutant IDH1 to mutant IDH2 or vice versa, thereby restoring 2HG production by the tumor. alpha-hydroxyglutarate 180-183 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 77-80 30355724-5 2018 SIGNIFICANCE: IDH-mutant cancers can develop resistance to isoform-selective IDH inhibition by "isoform switching" from mutant IDH1 to mutant IDH2 or vice versa, thereby restoring 2HG production by the tumor. alpha-hydroxyglutarate 180-183 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 127-131 30003571-2 2018 IDH1 mutations are associated with the accumulation of the oncometabolite D-2-hydroxyglutarate, which acts as an epigenetic modifier, and the development of multiple malignancies. alpha-hydroxyglutarate 74-94 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 30506321-2 2018 Somatic point mutations in IDH1/2 confer a gain-of-function in cancer cells, resulting in overproduction of an oncometabolite, 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 127-145 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-31 30020513-0 2018 2-Hydroxyglutarate MR spectroscopy for prediction of isocitrate dehydrogenase mutant glioma: a systemic review and meta-analysis using individual patient data. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 53-77 30020513-2 2018 We aimed to investigate the diagnostic performance of 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) for prediction of IDH mutant glioma and provide an optimal cutoff value for 2HG. alpha-hydroxyglutarate 54-72 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 135-138 30404018-0 2018 Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Cells. alpha-hydroxyglutarate 77-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 15-19 29847930-2 2018 However, mutant IDH1/2 (mIDH1/2) reduces alpha-KG to the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 72-90 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 16-22 30366412-9 2018 Therefore, we have determined that lipid anabolism is strongly reprogrammed in IDH1 mutant AML cells with a crucial dysregulation of fatty acid metabolism and fluxes, both being mediated by 2-HG (2-Hydroxyglutarate) production. alpha-hydroxyglutarate 196-214 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 79-83 30355481-0 2018 Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Sells. alpha-hydroxyglutarate 77-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 15-19 30405699-3 2018 Gain of function mutations in IDH1 or IDH2 result in reduced levels of alpha-KG as a result of increased formation of D-2-Hydroxyglutarate (2-HG). alpha-hydroxyglutarate 118-138 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 30249606-2 2018 Most tumor-relevant IDH1 mutations are deficient in the normal oxidization of isocitrate to alpha-ketoglutarate (alphaKG), but gain the neomorphic activity of reducing alphaKG to D-2-hydroxyglutarate (D2HG), which drives tumorigenesis. alpha-hydroxyglutarate 179-199 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 30305430-6 2018 Moreover, IDH1 R132H was a crucial modulator of 2-hydroxyglutarate, whose production from cells with IDH1 mutation promoted the binding of DNA-methyltransferase 1 (DNMT1) to the Fibulin-5 promoter, leading to its methylation. alpha-hydroxyglutarate 48-66 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-14 30305430-6 2018 Moreover, IDH1 R132H was a crucial modulator of 2-hydroxyglutarate, whose production from cells with IDH1 mutation promoted the binding of DNA-methyltransferase 1 (DNMT1) to the Fibulin-5 promoter, leading to its methylation. alpha-hydroxyglutarate 48-66 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 101-105 30113716-3 2018 Evaluation of the biological activities at the cellular level showed that compounds 11a, 11c, 11e, 11g, and 11s could effectively suppress the production of 2-hydroxyglutaric acid in U87MG cells expressing IDH1/R132H. alpha-hydroxyglutarate 157-179 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 206-210 30192797-8 2018 RESULTS: 2-hydroxyglutarate, an oncometabolite associated with gliomas with IDH mutations, was successfully detected and assigned by both 1H-13C HSQC and 1H-1H COSY experiments as well as 1H 1D experiments in two of the tissue samples. alpha-hydroxyglutarate 9-27 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 76-79 30194083-3 2018 IDH1 and IDH2 mutations are restricted to specific arginine residues in the active site of the enzymes and are gain-of-function, i.e. they confer a neomorphic enzyme activity resulting in the accumulation of D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 208-228 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 30209701-2 2018 The mutated form of the IDH1 enzyme produces a metabolite, 2-hydroxyglutarate (2-HG), which is thought to play a role in the formation and progression of acute myeloid leukaemia (AML), gliomas and other cancers. alpha-hydroxyglutarate 59-77 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-28 30209701-2 2018 The mutated form of the IDH1 enzyme produces a metabolite, 2-hydroxyglutarate (2-HG), which is thought to play a role in the formation and progression of acute myeloid leukaemia (AML), gliomas and other cancers. alpha-hydroxyglutarate 79-83 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-28 29805076-2 2018 Mutant IDH proteins acquire a neomorphic enzyme activity to produce the putative oncometabolite D-2-hydroxyglutarate, which is thought to block cellular differentiation by competitively inhibiting alpha-ketoglutarate-dependent dioxygenases involved in histone and DNA demethylation. alpha-hydroxyglutarate 96-116 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 29438510-1 2018 Background: Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2HG) in gliomas that can be detected by MRS. We examined the diagnostic accuracy of 2HG single-voxel spectroscopy (SVS) and chemical shift imaging (CSI) in both newly diagnosed and posttreatment settings. alpha-hydroxyglutarate 88-106 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-36 29438510-1 2018 Background: Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2HG) in gliomas that can be detected by MRS. We examined the diagnostic accuracy of 2HG single-voxel spectroscopy (SVS) and chemical shift imaging (CSI) in both newly diagnosed and posttreatment settings. alpha-hydroxyglutarate 88-106 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-41 29988124-1 2018 The oncometabolite (R)-2-hydroxyglutarate (R-2-HG) produced by isocitrate dehydrogenase (IDH) mutations promotes gliomagenesis via DNA and histone methylation. alpha-hydroxyglutarate 19-41 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 63-87 29988124-1 2018 The oncometabolite (R)-2-hydroxyglutarate (R-2-HG) produced by isocitrate dehydrogenase (IDH) mutations promotes gliomagenesis via DNA and histone methylation. alpha-hydroxyglutarate 19-41 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 89-92 29126125-2 2018 The goals of this study were to evaluate the performance of noninvasive magnetic resonance spectroscopy (MRS) methods to determine the IDH status of patients with brain gliomas through detection of the oncometabolite 2-hydroxyglutarate (2HG) and to compare performance of these methods with DNA sequencing and tissue 2HG analysis. alpha-hydroxyglutarate 217-235 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 135-138 29879375-2 2018 Mutated IDH1 (IDH1MUT) enzymes consume NADPH to produce d-2-hydroxyglutarate (d-2HG) resulting in the decreased reducing power needed for detoxification of reactive oxygen species (ROS), for example. alpha-hydroxyglutarate 56-76 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 8-12 29879375-2 2018 Mutated IDH1 (IDH1MUT) enzymes consume NADPH to produce d-2-hydroxyglutarate (d-2HG) resulting in the decreased reducing power needed for detoxification of reactive oxygen species (ROS), for example. alpha-hydroxyglutarate 56-76 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-21 29545476-1 2018 Mutant isocitrate dehydrogenase (IDH) 1/2 converts alpha-ketoglutarate (alpha-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit alpha-KG-dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. alpha-hydroxyglutarate 85-105 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 33-36 29545476-1 2018 Mutant isocitrate dehydrogenase (IDH) 1/2 converts alpha-ketoglutarate (alpha-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit alpha-KG-dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. alpha-hydroxyglutarate 107-113 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 33-36 29651790-2 2018 Mutations in position R132 trigger cancer by enabling IDH1 to produce D-2-hydroxyglutarate (2-HG) and reduce inhibition by ICT. alpha-hydroxyglutarate 70-90 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 54-58 29651790-2 2018 Mutations in position R132 trigger cancer by enabling IDH1 to produce D-2-hydroxyglutarate (2-HG) and reduce inhibition by ICT. alpha-hydroxyglutarate 92-96 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 54-58 29358170-3 2018 Nonetheless, we show here that, in mutant isocitrate dehydrogenase 1 (IDHmut) gliomas, which produce the oncometabolite 2-hydroxyglutarate (2-HG), PtdCho and PtdE biosynthesis is downregulated and results in lower levels of both phospholipids when compared with wild-type IDH1 cells. alpha-hydroxyglutarate 120-138 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 272-276 29719265-4 2018 Immortal astrocytes expressing IDH1R132H exhibited elevated (R)-2-hydroxyglutarate levels, reduced NADPH, increased proliferation, and anchorage-independent growth. alpha-hydroxyglutarate 60-82 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 31-35 29287025-0 2018 2-Hydroxyglutarate Detection by Short Echo Time Magnetic Resonance Spectroscopy in Routine Imaging Study of Brain Glioma at 3.0 T. OBJECTIVE: The objective of this study was to assess the effective performance of short echo time magnetic resonance spectroscopy (short TE MRS) for 2HG detection as biomarker of isocitrate dehydrogenase (IDH) status in all grade glioma (GL). alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 310-334 29287025-0 2018 2-Hydroxyglutarate Detection by Short Echo Time Magnetic Resonance Spectroscopy in Routine Imaging Study of Brain Glioma at 3.0 T. OBJECTIVE: The objective of this study was to assess the effective performance of short echo time magnetic resonance spectroscopy (short TE MRS) for 2HG detection as biomarker of isocitrate dehydrogenase (IDH) status in all grade glioma (GL). alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 336-339 29662077-0 2018 Pharmacodynamics of mutant-IDH1 inhibitors in glioma patients probed by in vivo 3D MRS imaging of 2-hydroxyglutarate. alpha-hydroxyglutarate 98-116 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-31 29522955-0 2018 Validation of a routine gas chromatography mass spectrometry method for 2-hydroxyglutarate quantification in human serum as a screening tool for detection of idh mutations. alpha-hydroxyglutarate 72-90 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 158-161 29522955-1 2018 High circulating levels of 2-hydroxyglutarate (2HG) have been reported in patients with determinate isocitrate dehydrogenase (IDH) mutated tumors. alpha-hydroxyglutarate 27-45 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 126-129 29619216-0 2018 Mutant IDH1 gliomas downregulate phosphocholine and phosphoethanolamine synthesis in a 2-hydroxyglutarate-dependent manner. alpha-hydroxyglutarate 87-105 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 29671246-3 2018 To establish a method for intraoperative molecular diagnosis, a simple, rapid method was developed for the measurement of 2-hydroxyglutarate (2-HG), a specific oncometabolite formed in the presence of IDH gene mutation, using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). alpha-hydroxyglutarate 122-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 201-204 29339439-2 2018 IDH1/2MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increased DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. alpha-hydroxyglutarate 26-46 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 29339439-2 2018 IDH1/2MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increased DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. alpha-hydroxyglutarate 48-52 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 29543066-2 2018 Mutations in IDH1 or IDH2 are detected in approximately 20% of patients with acute myeloid leukemia (AML) and induce amino acid changes in conserved residues resulting in neomorphic enzymatic function and production of an oncometabolite, 2-hydroxyglutarate (R-2-HG). alpha-hydroxyglutarate 238-256 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 29339836-3 2018 IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate. alpha-hydroxyglutarate 67-89 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 28956184-0 2018 Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy. alpha-hydroxyglutarate 49-67 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 22-25 28956184-1 2018 We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). alpha-hydroxyglutarate 55-73 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 83-107 28956184-1 2018 We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). alpha-hydroxyglutarate 55-73 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 109-112 29367755-2 2018 IDH1/2 mutations are causal in the development and/or progression of various types of cancer due to supraphysiological production of D-2-hydroxyglutarate. alpha-hydroxyglutarate 133-153 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 29643764-0 2018 The IDH1 Mutation-Induced Oncometabolite, 2-Hydroxyglutarate, May Affect DNA Methylation and Expression of PD-L1 in Gliomas. alpha-hydroxyglutarate 42-60 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-8 29643764-7 2018 A key product of the IDH1 mutation (2-hydroxyglutarate) was found to transiently increase DNA methylation and suppress PD-L1 expression. alpha-hydroxyglutarate 36-54 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-25 29900057-1 2018 D-2-hydroxyglutarate (D-2HG) is released by various types of malignant cells including acute myeloid leukemia (AML) blasts carrying isocitrate dehydrogenase (IDH) gain-of-function mutations. alpha-hydroxyglutarate 0-20 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 132-156 29900057-1 2018 D-2-hydroxyglutarate (D-2HG) is released by various types of malignant cells including acute myeloid leukemia (AML) blasts carrying isocitrate dehydrogenase (IDH) gain-of-function mutations. alpha-hydroxyglutarate 0-20 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 158-161 29547090-3 2018 Mutant IDH produces 2-hydroxyglutarate from alpha-ketoglutarate, a key metabolite of the Krebs cycle. alpha-hydroxyglutarate 20-38 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 29499756-0 2018 Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry. alpha-hydroxyglutarate 19-37 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 60-63 29499756-1 2018 All isocitrate dehydrogenase (IDH) mutant solid neoplasms exhibit highly elevated levels of D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 92-112 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-33 29315915-1 2018 Abnormally high levels of the "oncometabolite" 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. alpha-hydroxyglutarate 47-65 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 158-182 29315915-1 2018 Abnormally high levels of the "oncometabolite" 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. alpha-hydroxyglutarate 47-65 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 184-187 29315915-1 2018 Abnormally high levels of the "oncometabolite" 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. alpha-hydroxyglutarate 67-71 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 158-182 29315915-1 2018 Abnormally high levels of the "oncometabolite" 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. alpha-hydroxyglutarate 67-71 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 184-187 29439493-1 2018 Isocitrate dehydrogenases 1 and 2 (IDH1,2), the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs) and gain an unusual new activity of reducing the alpha-ketoglutarate (alpha-KG) to D-2 hydroxyglutarate (D-2HG) in a NADPH-consuming reaction. alpha-hydroxyglutarate 311-331 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-41 29288440-3 2018 Cells harboring IDH1 R132H -heterozygous mutation produce 2-hydroxyglutarate (2-HG), which results in histone and DNA hypermethylation. alpha-hydroxyglutarate 58-76 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 16-20 29288440-3 2018 Cells harboring IDH1 R132H -heterozygous mutation produce 2-hydroxyglutarate (2-HG), which results in histone and DNA hypermethylation. alpha-hydroxyglutarate 78-82 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 16-20 29274619-3 2018 The mutant forms of IDH1/2 catalyse the non-reversible accumulation of 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 71-89 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 28298040-2 2018 The objective of this study was to evaluate the clinical feasibility of using a recently described method for determining IDH mutation status by using magnetic resonance spectroscopy (MRS) to detect the presence of 2-hydroxyglutarate (2HG), the metabolic product of the mutant IDH enzyme. alpha-hydroxyglutarate 215-233 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 277-280 29331887-2 2018 Mutations in isocitrate dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. alpha-hydroxyglutarate 115-133 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-37 29331887-2 2018 Mutations in isocitrate dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. alpha-hydroxyglutarate 115-133 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 39-42 29458964-1 2018 Isocitrate dehydrogenases (IDH1/2) are frequently mutated in multiple types of human cancer, resulting in neomorphic enzymes that convert alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 172-190 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-33 29382206-3 2018 Owing to a mutation in an important arginine residue in the catalytic pocket, mutant IDH1 catalyzes the production of 2-hydroxyglutarate (2-HG) instead of its wild type product alpha-ketoglutarate (alpha-KG), which is involved in multiple cellular pathways involving the hydroxylation of proteins, ribonucleic acid, and deoxyribose nucleic acid (DNA). alpha-hydroxyglutarate 118-136 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 85-89 29670690-1 2018 Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. alpha-hydroxyglutarate 218-238 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 132-136 29670690-1 2018 Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. alpha-hydroxyglutarate 240-244 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 132-136 30783384-2 2018 Indeed, 70% of gliomas are associated with a gain-of-function IDH mutation and consequently synthesize the oncometabolite, 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 123-141 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 62-65 29089260-4 2017 All tested compounds effectively suppress the D-2-hydroxyglutarate (D-2-HG) production in cells transfected with IDH1-R132H and IDH1-R132C mutations at 10 muM and 50 muM. alpha-hydroxyglutarate 46-66 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 113-117 29089260-4 2017 All tested compounds effectively suppress the D-2-hydroxyglutarate (D-2-HG) production in cells transfected with IDH1-R132H and IDH1-R132C mutations at 10 muM and 50 muM. alpha-hydroxyglutarate 46-66 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 128-132 29089260-4 2017 All tested compounds effectively suppress the D-2-hydroxyglutarate (D-2-HG) production in cells transfected with IDH1-R132H and IDH1-R132C mutations at 10 muM and 50 muM. alpha-hydroxyglutarate 68-74 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 113-117 29089260-4 2017 All tested compounds effectively suppress the D-2-hydroxyglutarate (D-2-HG) production in cells transfected with IDH1-R132H and IDH1-R132C mutations at 10 muM and 50 muM. alpha-hydroxyglutarate 68-74 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 128-132 29056515-0 2017 In Vivo Imaging of Glutamine Metabolism to the Oncometabolite 2-Hydroxyglutarate in IDH1/2 Mutant Tumors. alpha-hydroxyglutarate 62-80 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 84-88 29056515-1 2017 The oncometabolite 2-hydroxyglutarate (2-HG) is a signature biomarker in various cancers, where it accumulates as a result of mutations in isocitrate dehydrogenase (IDH). alpha-hydroxyglutarate 19-37 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 139-163 29056515-1 2017 The oncometabolite 2-hydroxyglutarate (2-HG) is a signature biomarker in various cancers, where it accumulates as a result of mutations in isocitrate dehydrogenase (IDH). alpha-hydroxyglutarate 19-37 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 165-168 29056515-1 2017 The oncometabolite 2-hydroxyglutarate (2-HG) is a signature biomarker in various cancers, where it accumulates as a result of mutations in isocitrate dehydrogenase (IDH). alpha-hydroxyglutarate 39-43 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 139-163 29056515-1 2017 The oncometabolite 2-hydroxyglutarate (2-HG) is a signature biomarker in various cancers, where it accumulates as a result of mutations in isocitrate dehydrogenase (IDH). alpha-hydroxyglutarate 39-43 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 165-168 28986582-1 2017 Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that are mutated in a variety of cancers to confer a gain-of-function activity resulting in the accumulation of an oncometabolite, D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 206-226 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-38 28916733-2 2017 Mutant IDH1 drives overproduction of the oncometabolite d-2-hydroxyglutarate (2HG) and a CpG island (CGI) hypermethylation phenotype (G-CIMP). alpha-hydroxyglutarate 56-76 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 28232670-1 2017 Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are frequently found in several human cancer types including acute myeloid leukemia (AML) and lead to the production of high levels of the oncometabolite (R)-2-hydroxyglutarate (R-2HG). alpha-hydroxyglutarate 212-234 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-50 28232670-1 2017 Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are frequently found in several human cancer types including acute myeloid leukemia (AML) and lead to the production of high levels of the oncometabolite (R)-2-hydroxyglutarate (R-2HG). alpha-hydroxyglutarate 212-234 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 52-56 31225434-2 2017 The inhibition of TET enzymes by D-2-hydroxyglutarate (D-2-HG), which is produced by mutant IDH1/2 (mIDH1/2), has been suggested to promote epigenetic deregulation during tumorigenesis. alpha-hydroxyglutarate 33-53 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 92-98 31225434-2 2017 The inhibition of TET enzymes by D-2-hydroxyglutarate (D-2-HG), which is produced by mutant IDH1/2 (mIDH1/2), has been suggested to promote epigenetic deregulation during tumorigenesis. alpha-hydroxyglutarate 55-61 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 92-98 28315358-3 2017 The altered IDH protein leads to accumulation of 2-hydroxyglutarate (2-HG), a metabolite with oncogenic activity via epigenetic mechanisms. alpha-hydroxyglutarate 49-67 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-15 28315358-3 2017 The altered IDH protein leads to accumulation of 2-hydroxyglutarate (2-HG), a metabolite with oncogenic activity via epigenetic mechanisms. alpha-hydroxyglutarate 69-73 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-15 28467784-1 2017 Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts alpha-ketoglutarate (alpha-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 208-228 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-47 28467784-1 2017 Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts alpha-ketoglutarate (alpha-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 208-228 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 49-53 28467784-1 2017 Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts alpha-ketoglutarate (alpha-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 230-236 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-47 28467784-1 2017 Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts alpha-ketoglutarate (alpha-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 230-236 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 49-53 28653623-0 2017 Replication Study: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. alpha-hydroxyglutarate 151-169 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 61-65 28653623-1 2017 In 2016, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Fiehn et al., 2016), that described how we intended to replicate selected experiments from the paper "The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate" (Ward et al., 2010). alpha-hydroxyglutarate 333-351 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 243-247 28375741-3 2017 Several biochemical and genetic observations led to the discovery of the neomorphic production of the oncometabolite (R)-2-hydroxyglutarate (2-HG) by mutant IDH1 and IDH2 (mIDH). alpha-hydroxyglutarate 117-139 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 157-161 28629182-0 2017 Magnetic Resonance Spectroscopy for Detection of 2-Hydroxyglutarate as a Biomarker for IDH Mutation in Gliomas. alpha-hydroxyglutarate 49-67 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 87-90 28601826-4 2017 IDH1/2-mutated cancer cells produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine. alpha-hydroxyglutarate 55-75 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 28578659-0 2017 Rapamycin (mTORC1 inhibitor) reduces the production of lactate and 2-hydroxyglutarate oncometabolites in IDH1 mutant fibrosarcoma cells. alpha-hydroxyglutarate 67-85 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 105-109 28578659-1 2017 BACKGROUND: Multiple studies concluded that oncometabolites (e.g. D-2-hydroxyglutarate (2-HG) related to mutant isocitrate dehydrogenase 1/2 (IDH1/2) and lactate) have tumour promoting potential. alpha-hydroxyglutarate 68-86 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 142-148 28705010-3 2017 IDH mutations involve the catalytic pocket of the enzyme and lead to a neomorphic ability to produce 2-hydroxyglutarate (2HG) while oxidizing NADPH to NADP+. alpha-hydroxyglutarate 101-119 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 28497806-5 2017 Seizures often herald the diagnosis, especially in patients who have IDH mutations, which are associated with an increased production of 2-hydroxyglutarate. alpha-hydroxyglutarate 137-155 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 69-72 28330869-4 2017 IDH1 mutations typically result in a loss of catalytic activity, but many also can catalyze a new reaction, the NADPH-dependent reduction of alphaKG to d-2-hydroxyglutarate (D2HG). alpha-hydroxyglutarate 152-172 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 26945443-2 2017 The direct methods to detect IDH mutations include DNA sequencing, immunohistochemistry (IHC), or by measuring its byproduct, 2-hydroxyglutarate (2-HG), in the blood or urine. alpha-hydroxyglutarate 126-144 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 29-32 28193778-1 2017 Somatic gain-of-function mutations in isocitrate dehydrogenases (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite (R)-2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 176-198 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-77 28319049-5 2017 They show that the oncometabolite 2-hydroxyglutarate (2HG), generated by mutated forms of isocitrate dehydrogenase (IDH1 and IDH2), reduces the expression of STAT1, thereby limiting the production of the chemokines CXCL9 and CXCL10. alpha-hydroxyglutarate 34-52 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 116-120 27721426-6 2017 Mutant IDH enzymes have neomorphic activity and catalyze reduction of alpha-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked differentiation of hematopoietic progenitor cells. alpha-hydroxyglutarate 104-122 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 28148839-0 2017 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-45 28052098-7 2017 Mutations in isocitrate dehydrogenase (IDH) 1 also change the function of the enzymes and cause them to produce 2-hydroxyglutarate and not produce NADPH. alpha-hydroxyglutarate 112-130 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-45 27852048-2 2017 Mutant IDH produces (R)-2-hydroxyglutarate, which induces DNA hypermethylation and presumably drives tumorigenesis. alpha-hydroxyglutarate 20-42 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 28735490-3 2017 The measurement of D-2-hydroxyglutarate in peripheral blood may be used as a biomarker for screening and follow-up of patients with IDH-mutated acute myeloid leukemia. alpha-hydroxyglutarate 19-39 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 132-135 27956631-1 2016 Oncogenic isocitrate dehydrogenase (IDH)1 and IDH2 mutations at three hotspot arginine residues cause an enzymatic gain of function that leads to the production and accumulation of the metabolite 2-hydroxyglutarate (2HG), which contributes to the development of a number of malignancies. alpha-hydroxyglutarate 196-214 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-41 27340277-0 2016 Selective Detection of the D-enantiomer of 2-Hydroxyglutarate in the CSF of Glioma Patients with Mutated Isocitrate Dehydrogenase. alpha-hydroxyglutarate 43-61 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 105-129 27340277-1 2016 PURPOSE: Elevation in D-2-Hydroxyglutarate (D-2HG) has recently emerged as a mandatory byproduct of mutated Isocitrate Dehydrogenase (IDH) genes 1 and 2 in glioma patients. alpha-hydroxyglutarate 22-42 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 108-132 27340277-1 2016 PURPOSE: Elevation in D-2-Hydroxyglutarate (D-2HG) has recently emerged as a mandatory byproduct of mutated Isocitrate Dehydrogenase (IDH) genes 1 and 2 in glioma patients. alpha-hydroxyglutarate 22-42 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 134-137 27664011-1 2016 Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 76-96 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 27664011-1 2016 Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 98-104 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 28248126-0 2016 Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH-Mutant Glioma. alpha-hydroxyglutarate 37-55 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 158-161 28248126-1 2016 Purpose Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase ( IDH). alpha-hydroxyglutarate 77-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 188-212 28248126-1 2016 Purpose Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase ( IDH). alpha-hydroxyglutarate 77-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 215-218 27758882-1 2016 Mutations in the isocitrate dehydrogenase gene IDH1 are common in low-grade glioma, where they result in the production of 2-hydroxyglutarate (2HG), disrupted patterns of histone methylation, and gliomagenesis. alpha-hydroxyglutarate 123-141 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-51 27154922-0 2016 Diagnostic value of glutamate with 2-hydroxyglutarate in magnetic resonance spectroscopy for IDH1 mutant glioma. alpha-hydroxyglutarate 35-53 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 93-97 27154922-1 2016 BACKGROUND: Mutations in the isocitrate dehydrogenase 1 (IDH1) gene that are frequently observed in low-grade glioma are strongly associated with the accumulation of 2-hydroxyglutarate (2HG), which is a valuable diagnostic and prognostic biomarker of IDH1 mutant glioma. alpha-hydroxyglutarate 166-184 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 29-55 27154922-1 2016 BACKGROUND: Mutations in the isocitrate dehydrogenase 1 (IDH1) gene that are frequently observed in low-grade glioma are strongly associated with the accumulation of 2-hydroxyglutarate (2HG), which is a valuable diagnostic and prognostic biomarker of IDH1 mutant glioma. alpha-hydroxyglutarate 166-184 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 57-61 27154922-1 2016 BACKGROUND: Mutations in the isocitrate dehydrogenase 1 (IDH1) gene that are frequently observed in low-grade glioma are strongly associated with the accumulation of 2-hydroxyglutarate (2HG), which is a valuable diagnostic and prognostic biomarker of IDH1 mutant glioma. alpha-hydroxyglutarate 166-184 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 251-255 27382115-1 2016 BACKGROUND: Gliomas with mutant isocitrate dehydrogenase (IDH) produce high levels of 2-hydroxyglutarate (2HG) that can be quantitatively measured by 3D magnetic resonance spectroscopic imaging (MRSI). alpha-hydroxyglutarate 86-104 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-56 27382115-1 2016 BACKGROUND: Gliomas with mutant isocitrate dehydrogenase (IDH) produce high levels of 2-hydroxyglutarate (2HG) that can be quantitatively measured by 3D magnetic resonance spectroscopic imaging (MRSI). alpha-hydroxyglutarate 86-104 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 58-61 27380194-5 2016 Additionally, the mutation of isocitrate dehydrogenase (IDH), the enzyme downstream of ACO1 in the TCA cycle, is associated with epigenetic abnormalities secondary to 2-hydroxyglutarate (2-HG) and DNA methylation. alpha-hydroxyglutarate 167-185 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-54 27380194-5 2016 Additionally, the mutation of isocitrate dehydrogenase (IDH), the enzyme downstream of ACO1 in the TCA cycle, is associated with epigenetic abnormalities secondary to 2-hydroxyglutarate (2-HG) and DNA methylation. alpha-hydroxyglutarate 167-185 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 56-59 27430238-2 2016 IDH1 mutations lead to the formation of the oncometabolite 2-hydroxyglutarate (2-HG) from the reduction of alpha-ketoglutarate (alpha-KG), which in turn facilitates tumorigenesis by modifying DNA and histone methylation as well blocking differentiation processes. alpha-hydroxyglutarate 59-77 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 27659543-0 2016 Non-invasive detection of 2-hydroxyglutarate in IDH-mutated gliomas using two-dimensional localized correlation spectroscopy (2D L-COSY) at 7 Tesla. alpha-hydroxyglutarate 26-44 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 48-51 27621679-3 2016 Somatic point mutations in IDH1/2 confer a gain-of-function in cancer cells, resulting in the accumulation and secretion in vast excess of an oncometabolite, the D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 162-182 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-31 27587950-0 2016 In-Vivo Proton Magnetic Resonance Spectroscopy of 2-Hydroxyglutarate in Isocitrate Dehydrogenase-Mutated Gliomas: A Technical Review for Neuroradiologists. alpha-hydroxyglutarate 50-68 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 72-96 27587950-1 2016 The diagnostic and prognostic potential of an onco-metabolite, 2-hydroxyglutarate (2HG) as a proton magnetic resonance spectroscopy (1H-MRS) detectable biomarker of the isocitrate dehydrogenase (IDH)-mutated (IDH-MT) gliomas has drawn attention of neuroradiologists recently. alpha-hydroxyglutarate 63-81 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 169-193 27587950-1 2016 The diagnostic and prognostic potential of an onco-metabolite, 2-hydroxyglutarate (2HG) as a proton magnetic resonance spectroscopy (1H-MRS) detectable biomarker of the isocitrate dehydrogenase (IDH)-mutated (IDH-MT) gliomas has drawn attention of neuroradiologists recently. alpha-hydroxyglutarate 63-81 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 195-198 27354064-5 2016 Neomorphic mutations in IDH1 occur frequently in certain cancers, leading to the production of the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 114-132 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-28 27063596-0 2016 Enantiomer-specific and paracrine leukemogenicity of mutant IDH metabolite 2-hydroxyglutarate. alpha-hydroxyglutarate 75-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 60-63 27063596-1 2016 Canonical mutations in IDH1 and IDH2 produce high levels of the R-enantiomer of 2-hydroxyglutarate (R-2HG), which is a competitive inhibitor of alpha-ketoglutarate (alphaKG)-dependent enzymes and a putative oncometabolite. alpha-hydroxyglutarate 80-98 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-27 27431380-4 2016 Mutant IDH enzymes produce high levels of the oncometabolite (R)-2-hydroxyglutarate that competitively inhibits dioxygenase enzymes that modify methylcytosine to hydroxymethylcytosine and histone tail methylation. alpha-hydroxyglutarate 61-83 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 27131892-0 2016 Quantitation of isocitrate dehydrogenase (IDH)-induced D and L enantiomers of 2-hydroxyglutaric acid in biological fluids by a fully validated liquid tandem mass spectrometry method, suitable for clinical applications. alpha-hydroxyglutarate 78-100 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 16-40 27131892-0 2016 Quantitation of isocitrate dehydrogenase (IDH)-induced D and L enantiomers of 2-hydroxyglutaric acid in biological fluids by a fully validated liquid tandem mass spectrometry method, suitable for clinical applications. alpha-hydroxyglutarate 78-100 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-45 27131892-2 2016 Activating mutations in isocitrate dehydrogenase (IDH) metabolic enzymes leading to the abnormal accumulation of 2-hydroxyglutaric acid (2-HGA) have been described in hematologic malignancies and solid tumours. alpha-hydroxyglutarate 113-135 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-48 27131892-2 2016 Activating mutations in isocitrate dehydrogenase (IDH) metabolic enzymes leading to the abnormal accumulation of 2-hydroxyglutaric acid (2-HGA) have been described in hematologic malignancies and solid tumours. alpha-hydroxyglutarate 113-135 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 50-53 27547821-1 2016 2-hydroxyglutarate (2-HG) has emerged as a biomarker of tumour cell IDH mutations that may enable the differential diagnosis of glioma patients. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 68-71 27355333-3 2016 The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG) by NADPH. alpha-hydroxyglutarate 143-161 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-16 27005468-3 2016 IDH1 and IDH2 mutations confer neomorphic activity in the mutant protein, resulting in the conversion of alphaKG to the oncometabolite, D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 136-156 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 26534967-0 2016 Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate. alpha-hydroxyglutarate 114-132 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 33-36 26534967-2 2016 The hallmark metabolic alteration in gliomas with mutant isocitrate dehydrogenase (IDH) is the overproduction of oncometabolite 2-hydroxyglutarate (2HG), which plays a key role in malignant transformation. alpha-hydroxyglutarate 128-146 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 57-81 26534967-2 2016 The hallmark metabolic alteration in gliomas with mutant isocitrate dehydrogenase (IDH) is the overproduction of oncometabolite 2-hydroxyglutarate (2HG), which plays a key role in malignant transformation. alpha-hydroxyglutarate 128-146 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 83-86 26582645-0 2016 Pretreatment d-2-hydroxyglutarate serum levels negatively impact on outcome in IDH1-mutated acute myeloid leukemia. alpha-hydroxyglutarate 13-33 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 79-83 26582645-1 2016 Mutations in isocitrate dehydrogenases (IDHs) 1 and 2 frequently occur in acute myeloid leukemia (AML) and result in the production of the oncometabolite d-2-hydroxyglutarate (D2HG). alpha-hydroxyglutarate 154-174 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-53 26985452-2 2016 Mutant IDH1 catalyzes production of the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 55-73 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 26971564-5 2016 Lu and colleagues demonstrated that expression of mutant forms of IDH1 or IDH2 caused global increases in histone methylation and increased levels of 2 hydroxyglutarate (Figure 1B). alpha-hydroxyglutarate 150-168 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-70 26856236-2 2016 2-Hydroxyglutarate (2HG) produced by mutant IDH alters the binding of the chromosomal organizer protein CTCF, disrupting the spatial and regulatory organization of the genome. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-47 26943899-0 2016 Registered report: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. alpha-hydroxyglutarate 151-169 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 61-65 26943899-3 2016 This Registered Report describes the proposed replication plan of key experiments from "The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate" by Ward and colleagues, published in Cancer Cell in 2010 (Ward et al., 2010). alpha-hydroxyglutarate 220-238 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 130-134 26691210-0 2016 Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma. alpha-hydroxyglutarate 15-33 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 122-146 26691210-4 2016 RESULTS: Detection of 2-hydroxyglutarate (2HG) in IDH-mutant gliomas was closely linked to tumor volume, with sensitivity ranging from 8% for small tumors (<3.4 mL) to 91% for larger tumors (>8 mL). alpha-hydroxyglutarate 22-40 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 50-53 26834160-0 2016 Elevation of Urinary 2-Hydroxyglutarate in IDH-Mutant Glioma. alpha-hydroxyglutarate 21-39 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 43-46 26834160-1 2016 BACKGROUND: Recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, which are frequent in gliomas, result in marked accumulation of the metabolic by-product 2-hydroxyglutarate (2-HG) within tumors. alpha-hydroxyglutarate 178-196 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 39-65 26834160-1 2016 BACKGROUND: Recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, which are frequent in gliomas, result in marked accumulation of the metabolic by-product 2-hydroxyglutarate (2-HG) within tumors. alpha-hydroxyglutarate 178-196 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 67-71 26858939-6 2016 Indeed, emerging research on the consequences of mutant IDH1 protein expression suggests that its neomorphic enzymatic activity catalyzing the production of the oncometabolite 2-hydroxyglutarate influences a range of cellular programs that affect the epigenome and contribute to glioblastoma development. alpha-hydroxyglutarate 176-194 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 56-60 26820720-1 2016 Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are frequently found in brain tumors, and the resulting onco-metabolite, 2-hydroxyglutarate (2HG), has been suggested to be a potential diagnostic and prognostic biomarker of the diseases. alpha-hydroxyglutarate 128-146 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-53 26700815-2 2016 Mutant IDH protein produces a new onco-metabolite, 2-hydroxyglutarate, which interferes with iron-dependent hydroxylases, including the TET family of 5"-methylcytosine hydroxylases. alpha-hydroxyglutarate 51-69 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 26669865-0 2016 Noninvasive Quantification of 2-Hydroxyglutarate in Human Gliomas with IDH1 and IDH2 Mutations. alpha-hydroxyglutarate 30-48 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 71-75 26669865-1 2016 Mutations in the isocitrate dehydrogenase genes (IDH1/2) occur often in diffuse gliomas, where they are associated with abnormal accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 164-182 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 49-55 26960449-4 2016 While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form alpha-ketoglutarate (alpha-KG), IDH1 and IDH2 mutations convert alpha-KG to 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 157-175 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 6-10 26960449-4 2016 While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form alpha-ketoglutarate (alpha-KG), IDH1 and IDH2 mutations convert alpha-KG to 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 157-175 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 113-117 26960449-4 2016 While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form alpha-ketoglutarate (alpha-KG), IDH1 and IDH2 mutations convert alpha-KG to 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 177-181 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 6-10 26960449-4 2016 While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form alpha-ketoglutarate (alpha-KG), IDH1 and IDH2 mutations convert alpha-KG to 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 177-181 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 113-117 27557538-8 2016 Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. alpha-hydroxyglutarate 14-32 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 74-98 27557538-8 2016 Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. alpha-hydroxyglutarate 14-32 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 100-103 27557538-8 2016 Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. alpha-hydroxyglutarate 14-32 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 259-262 27557538-8 2016 Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. alpha-hydroxyglutarate 34-38 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 74-98 27557538-8 2016 Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. alpha-hydroxyglutarate 34-38 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 100-103 27557538-8 2016 Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. alpha-hydroxyglutarate 34-38 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 259-262 26686626-0 2015 Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents. alpha-hydroxyglutarate 15-35 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 85-88 26686626-2 2015 The benefit of this regimen, known as PCV, was recently linked to IDH mutation that occurs frequently in glioma and produces D-2-hydroxyglutarate (D-2-HG), a competitive inhibitor of alpha-ketoglutarate (alpha-KG). alpha-hydroxyglutarate 125-145 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-69 26686626-2 2015 The benefit of this regimen, known as PCV, was recently linked to IDH mutation that occurs frequently in glioma and produces D-2-hydroxyglutarate (D-2-HG), a competitive inhibitor of alpha-ketoglutarate (alpha-KG). alpha-hydroxyglutarate 147-153 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-69 26678339-1 2015 Heterozygous mutation of IDH1 in cancers modifies IDH1 enzymatic activity, reprogramming metabolite flux and markedly elevating 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 128-146 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 25-29 26088953-0 2015 Direct comparison of quantitative digital PCR and 2-hydroxyglutarate enantiomeric ratio for IDH mutant allele frequency assessment in myeloid malignancy. alpha-hydroxyglutarate 50-68 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 92-95 26363012-1 2015 Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. alpha-hydroxyglutarate 187-207 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 26363012-1 2015 Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. alpha-hydroxyglutarate 187-207 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 26363012-1 2015 Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. alpha-hydroxyglutarate 187-207 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 81-85 26363012-5 2015 Exposure of IDH1 wild-type cells to D-2-hydroxyglutarate was sufficient to reduce IDH-mediated NADPH production and increase IR sensitivity. alpha-hydroxyglutarate 36-56 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-16 26363012-5 2015 Exposure of IDH1 wild-type cells to D-2-hydroxyglutarate was sufficient to reduce IDH-mediated NADPH production and increase IR sensitivity. alpha-hydroxyglutarate 36-56 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-15 26381180-2 2015 Although IDH1 catalyzes the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in cytosol, mutated IDH1 proteins possess the ability to change alpha-KG into the oncometabolite D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 197-217 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 9-13 26381180-2 2015 Although IDH1 catalyzes the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in cytosol, mutated IDH1 proteins possess the ability to change alpha-KG into the oncometabolite D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 197-217 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 120-124 26368816-0 2015 Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells. alpha-hydroxyglutarate 133-151 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 39-43 26280302-2 2015 With losing the activity of wild-type IDH1, the R132H and R132C mutant proteins can reduce alpha-ketoglutaric acid (alpha-KG) to d-2-hydroxyglutaric acid (D2HG). alpha-hydroxyglutarate 129-153 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-42 26617922-2 2015 Mutant IDH generates the oncometabolite D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 40-60 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 26212717-1 2015 Somatic mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2) contribute to the pathogenesis of cancer via production of the "oncometabolite" D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 142-162 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 54-60 26045167-1 2015 Mutant isocitrate dehydrogenase 1 (IDH1) catalyzes the production of 2-hydroxyglutarate but also elicits additional metabolic changes. alpha-hydroxyglutarate 69-87 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 26231040-4 2015 The key experiments being replicated include Supplemental Figure 3I, which demonstrates that transfection with mutant forms of IDH1 increases levels of 2-hydroxyglutarate (2-HG), Figures 3A and 8A, which demonstrate changes in histone methylation after treatment with 2-HG, and Figures 3D and 7B, which show that mutant IDH1 can effect the same changes as treatment with excess 2-HG. alpha-hydroxyglutarate 152-170 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 127-131 25908561-0 2015 Conditions for (13)C NMR detection of 2-hydroxyglutarate in tissue extracts from isocitrate dehydrogenase-mutated gliomas. alpha-hydroxyglutarate 38-56 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 81-105 25908561-2 2015 However, in isocitrate dehydrogenase (IDH)-mutant gliomas, (13)C labeling is obscured in oncometabolite 2-hydroxyglutaric acid (2 HG) by glutamate and glutamine, prompting development of a simple method to resolve the metabolites. alpha-hydroxyglutarate 104-126 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-41 26178471-2 2015 In cancer, mutant IDH1/2 reduces alpha-KG to D2-hydroxyglutarate (D2-HG) disrupting alpha-KG-dependent dioxygenases. alpha-hydroxyglutarate 45-64 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 18-22 26161668-1 2015 Somatic mutations in the isocitrate dehydrogenase (IDH)1/2 genes endow encoding proteins with neomorphic activity to produce the potential oncometabolite, 2-hydroxyglutarate (2-HG), which induces the hypermethylation of histones and DNA. alpha-hydroxyglutarate 155-173 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 51-58 26111463-3 2015 An intriguing aspect of IDH1/2-mutant malignancies is the aberrant production of the oncometabolite 2-hydroxyglutarate (2-HG), which likely play a pivotal oncogenic role. alpha-hydroxyglutarate 100-118 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-28 26046462-0 2015 The oncometabolite D-2-hydroxyglutarate induced by mutant IDH1 or -2 blocks osteoblast differentiation in vitro and in vivo. alpha-hydroxyglutarate 19-39 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 58-62 26046462-3 2015 The mutant IDH1/2 causes elevated levels of D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 44-64 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 11-15 26046462-3 2015 The mutant IDH1/2 causes elevated levels of D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 66-72 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 11-15 25651001-1 2015 Mutations in IDH1 and IDH2 occur in 15-20% of AML cases, resulting in the production of 2-hydroxyglutarate, which promotes aberrant hypermethylation of DNA in leukemic cells. alpha-hydroxyglutarate 88-106 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 26018518-2 2015 Dysfunctional IDH leads to reduced production of alpha-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. alpha-hydroxyglutarate 95-113 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-17 25862748-1 2015 BACKGROUND: Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert alpha-ketoglutarate into 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 99-117 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 19-53 25825982-0 2015 D-2-hydroxyglutarate is essential for maintaining oncogenic property of mutant IDH-containing cancer cells but dispensable for cell growth. alpha-hydroxyglutarate 0-20 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 79-82 25825982-1 2015 Cancer-associated isocitrate dehydrogenase (IDH) 1 and 2 mutations gain a new activity of reducing alpha-KG to produce D-2-hydroxyglutarate (D-2-HG), which is proposed to function as an oncometabolite by inhibiting alpha-KG dependent dioxygenases. alpha-hydroxyglutarate 119-139 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-47 25825982-1 2015 Cancer-associated isocitrate dehydrogenase (IDH) 1 and 2 mutations gain a new activity of reducing alpha-KG to produce D-2-hydroxyglutarate (D-2-HG), which is proposed to function as an oncometabolite by inhibiting alpha-KG dependent dioxygenases. alpha-hydroxyglutarate 141-147 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-47 25648147-4 2015 In cancer cells carrying mutant IDH1, FOXOs likewise stimulate mutant IDH1 expression and maintain the levels of the oncometabolite 2-hydroxyglutarate, which stimulates cancer cell proliferation and inhibits TET enzymes and histone demethylases. alpha-hydroxyglutarate 132-150 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-36 25586680-4 2015 The mutated forms of IDH1 and IDH2 produce an oncogenic metabolite, D-2-hydroxyglutarate (D2HG). alpha-hydroxyglutarate 68-88 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-25 25853107-6 2015 In addition, we have observed that IDH1-R132H was more efficient than IDH1 in converting alpha-KG into (R)-2-hydroxyglutarate (R-2HG). alpha-hydroxyglutarate 103-125 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 25853107-6 2015 In addition, we have observed that IDH1-R132H was more efficient than IDH1 in converting alpha-KG into (R)-2-hydroxyglutarate (R-2HG). alpha-hydroxyglutarate 103-125 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 70-74 25706986-2 2015 IDH1 is the enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate while mutant IDH1 catalyzes the conversion of alpha-ketoglutarate into 2-hydroxyglutarate. alpha-hydroxyglutarate 172-190 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 25706986-2 2015 IDH1 is the enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate while mutant IDH1 catalyzes the conversion of alpha-ketoglutarate into 2-hydroxyglutarate. alpha-hydroxyglutarate 172-190 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 114-118 25706986-11 2015 Specifically, a significant drop in the concentration of glutamate, lactate and phosphocholine as well as the expected elevation in 2-hydroxyglutarate were observed in mutant IDH1 cells when compared to their wild-type counterparts. alpha-hydroxyglutarate 132-150 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 175-179 25706986-12 2015 CONCLUSION: The IDH1 mutation leads to several, potentially translatable MRS-detectable metabolic changes beyond the production of 2-hydroxyglutarate. alpha-hydroxyglutarate 131-149 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 16-20 25481493-3 2015 Mutant IDH acquires neomorphic enzymatic activity to generate the oncometabolite d-2-hydroxyglutarate (d-2HG). alpha-hydroxyglutarate 81-101 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 25471051-1 2015 Mutations in isocitrate dehydrogenase 1 (IDH1) have been found in the vast majority of low grade and progressive infiltrating gliomas and are characterized by the production of 2-hydroxyglutarate from alpha-ketoglutarate. alpha-hydroxyglutarate 177-195 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-39 25471051-1 2015 Mutations in isocitrate dehydrogenase 1 (IDH1) have been found in the vast majority of low grade and progressive infiltrating gliomas and are characterized by the production of 2-hydroxyglutarate from alpha-ketoglutarate. alpha-hydroxyglutarate 177-195 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 41-45 25391653-1 2015 Cancer-associated point mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) confer a neomorphic enzymatic activity: the reduction of alpha-ketoglutarate to d-2-hydroxyglutaric acid, which is proposed to act as an oncogenic metabolite by inducing hypermethylation of histones and DNA. alpha-hydroxyglutarate 166-190 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 37-63 25391653-1 2015 Cancer-associated point mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) confer a neomorphic enzymatic activity: the reduction of alpha-ketoglutarate to d-2-hydroxyglutaric acid, which is proposed to act as an oncogenic metabolite by inducing hypermethylation of histones and DNA. alpha-hydroxyglutarate 166-190 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 71-75 25391653-3 2015 A high throughput screen for selective inhibitors of IDH1 bearing the oncogenic mutation R132H identified compound 1, a bis-imidazole phenol that inhibits d-2-hydroxyglutaric acid production in cells. alpha-hydroxyglutarate 155-179 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 53-57 25398939-1 2015 Gain-of-function mutations in nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase (IDH)1 and IDH2 frequently arise in human leukemias and other cancers and produce high levels of D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 206-226 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 110-115 25398940-1 2015 Mutations of IDH1 and IDH2, which produce the oncometabolite 2-hydroxyglutarate (2HG), have been identified in several tumors, including acute myeloid leukemia. alpha-hydroxyglutarate 61-79 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 25993236-7 2015 The normal IDH protein continues to produce alpha-ketoglutarate (alpha-KG) whereas the mutant IDH protein converts KG to the oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 140-158 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 94-97 25251602-1 2015 The R132H and R172K mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have neomorphic activity of generating 2-hydroxyglutarate (2-HG) which has been implicated in the oncogenesis. alpha-hydroxyglutarate 121-139 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 67-71 25251602-9 2015 The R132H and R172K mutations of isocitrate dehydrogenase 1 and 2, respectively, (IDH1 and IDH2) have neomorphic activity of generating 2-hydroxyglutarate (2-HG) which has been implicated in oncogenesis. alpha-hydroxyglutarate 136-154 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 82-86 25251602-9 2015 The R132H and R172K mutations of isocitrate dehydrogenase 1 and 2, respectively, (IDH1 and IDH2) have neomorphic activity of generating 2-hydroxyglutarate (2-HG) which has been implicated in oncogenesis. alpha-hydroxyglutarate 156-160 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 82-86 25502799-2 2014 Mutation of the catalytic Arg132 residue of human IDH1 (HcIDH) eliminates the enzyme"s wild-type isocitrate oxidation activity, but confer the mutant an ability of reducing alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 207-225 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 50-54 25502799-2 2014 Mutation of the catalytic Arg132 residue of human IDH1 (HcIDH) eliminates the enzyme"s wild-type isocitrate oxidation activity, but confer the mutant an ability of reducing alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 227-231 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 50-54 25078896-8 2014 IDH1/2 mutations are tightly associated with grade II and III gliomas and secondary glioblastomas, with better prognosis and production of a recently described oncometabolite, 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 176-194 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 25376594-1 2014 INTRODUCTION: Previous magnetic resonance spectroscopy (MRS) and mass spectroscopy studies have shown accumulation of 2-hydroxyglutarate (2HG) in mutant isocitrate dehydrogenase (IDH) gliomas. alpha-hydroxyglutarate 118-136 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 153-177 25376594-1 2014 INTRODUCTION: Previous magnetic resonance spectroscopy (MRS) and mass spectroscopy studies have shown accumulation of 2-hydroxyglutarate (2HG) in mutant isocitrate dehydrogenase (IDH) gliomas. alpha-hydroxyglutarate 118-136 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 179-182 25135281-4 2014 The metabolic product of mutant IDH1, D-2-hydroxyglutarate (2-HG), can suppress Par-4 transcription in vitro via inhibition of promoter activity as well as enhanced mRNA degradation, but interestingly not by direct DNA promoter hypermethylation. alpha-hydroxyglutarate 38-58 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-36 25135281-4 2014 The metabolic product of mutant IDH1, D-2-hydroxyglutarate (2-HG), can suppress Par-4 transcription in vitro via inhibition of promoter activity as well as enhanced mRNA degradation, but interestingly not by direct DNA promoter hypermethylation. alpha-hydroxyglutarate 60-64 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-36 25496513-3 2014 The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. alpha-hydroxyglutarate 113-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-30 25496513-3 2014 The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. alpha-hydroxyglutarate 113-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-36 25271760-2 2014 Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of alpha-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. alpha-hydroxyglutarate 112-136 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-38 25277207-0 2014 Mutations in CIC and IDH1 cooperatively regulate 2-hydroxyglutarate levels and cell clonogenicity. alpha-hydroxyglutarate 49-67 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-25 25005896-2 2014 IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. alpha-hydroxyglutarate 47-65 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 25040794-5 2014 The importance of the TET-mediated cytosine demethylation pathway is also underscored by a recurrent mutation of isocitrate dehydrogenase 1 (IDH1) and IDH2 in hematological malignancies, whose mutation inhibits TET function through a novel oncometabolite, 2-hydroxyglutarate. alpha-hydroxyglutarate 256-274 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 113-139 25040794-5 2014 The importance of the TET-mediated cytosine demethylation pathway is also underscored by a recurrent mutation of isocitrate dehydrogenase 1 (IDH1) and IDH2 in hematological malignancies, whose mutation inhibits TET function through a novel oncometabolite, 2-hydroxyglutarate. alpha-hydroxyglutarate 256-274 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 141-145 24903073-3 2014 The IDH1 mutation leads to the accumulation of 2-hydroxyglutarate (2HG), a metabolite that bears a close structural similarity to glutamate, an excitatory neurotransmitter that has been implicated in the pathogenesis of TAE. alpha-hydroxyglutarate 47-65 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-8 24980596-2 2014 The most frequent mutation, IDH1 R132H, is a gain-of-function mutation resulting in an enzyme-catalyzing conversion of alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 153-171 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 24986863-7 2014 Treatment of cells with a d-2-hydroxyglutarate (d-2HG) ester recapitulated these changes, indicating that the alterations observed in the knocked-in cells were mediated by d-2HG produced by the IDH1 mutant. alpha-hydroxyglutarate 26-46 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 194-198 24771584-8 2014 In support of a functional link between these molecules, in vitro expression of mutant IDH1 inhibited Akt phosphorylation in a 2-hydroxyglutarate-dependent manner. alpha-hydroxyglutarate 127-145 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 87-91 24606602-0 2014 Elevated plasma 2-hydroxyglutarate in acute myeloid leukaemia: association with the IDH1 SNP rs11554137 and severe renal impairment. alpha-hydroxyglutarate 16-34 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 84-88 24740997-1 2014 UNLABELLED: Recently identified isocitrate dehydrogenase (IDH) mutations lead to the production of 2-hydroxyglutarate (2HG), an oncometabolite aberrantly elevated in selected cancers. alpha-hydroxyglutarate 99-117 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-56 24740997-1 2014 UNLABELLED: Recently identified isocitrate dehydrogenase (IDH) mutations lead to the production of 2-hydroxyglutarate (2HG), an oncometabolite aberrantly elevated in selected cancers. alpha-hydroxyglutarate 99-117 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 58-61 24609756-7 2014 Biomarkers such as 2- hydroxyglutarate in IDH1/2-mutant AML patients predict patient responses and minimal residual disease. alpha-hydroxyglutarate 19-38 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-46 24549719-2 2014 Mutations of IDH1 and IDH2 lead to simultaneous loss and gain of activities in the production of alpha-ketoglutarate and 2-hydroxyglutarate, respectively. alpha-hydroxyglutarate 121-139 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 24760710-0 2014 Isocitrate dehydrogenase 1 (IDH1) mutation in breast adenocarcinoma is associated with elevated levels of serum and urine 2-hydroxyglutarate. alpha-hydroxyglutarate 122-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 24760710-0 2014 Isocitrate dehydrogenase 1 (IDH1) mutation in breast adenocarcinoma is associated with elevated levels of serum and urine 2-hydroxyglutarate. alpha-hydroxyglutarate 122-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 24760710-2 2014 An intriguing aspect of IDH-mutant tumors is the aberrant production and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which may play a pivotal oncogenic role in these malignancies. alpha-hydroxyglutarate 108-126 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-27 24590270-4 2014 Mutant IDH1 gains novel enzyme activity converting alpha-KG to D-2-hydroxyglutarate (2-HG) which acts as a competitive inhibitor of alpha-KG. alpha-hydroxyglutarate 63-83 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 24590270-4 2014 Mutant IDH1 gains novel enzyme activity converting alpha-KG to D-2-hydroxyglutarate (2-HG) which acts as a competitive inhibitor of alpha-KG. alpha-hydroxyglutarate 85-89 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 24366912-2 2014 However, recent experimental data have shown that production of 2-hydroxyglutarate by IDH mutant cells promotes hypoxia-inducible factor (HIF)1alpha degradation and, by doing so, may have unexpected metabolic effects. alpha-hydroxyglutarate 64-82 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 86-89 24478380-1 2014 PURPOSE: Mutations in the IDH1 and IDH2 (IDH1/2) genes occur in approximately 20% of intrahepatic cholangiocarcinoma and lead to accumulation of 2-hydroxyglutarate (2HG) in the tumor tissue. alpha-hydroxyglutarate 145-163 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-30 24440599-1 2014 Mutations in the metabolic enzymes isocitrate dehydrogenase-1 (IDH1) and IDH2 that produce the oncometabolite D-2-hydroxyglutarate (2-HG) occur frequently in human acute myeloid leukemia (AML). alpha-hydroxyglutarate 110-130 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-61 24440599-1 2014 Mutations in the metabolic enzymes isocitrate dehydrogenase-1 (IDH1) and IDH2 that produce the oncometabolite D-2-hydroxyglutarate (2-HG) occur frequently in human acute myeloid leukemia (AML). alpha-hydroxyglutarate 110-130 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 63-67 24529257-1 2014 BACKGROUND: IDH mutations frequently occur in diffuse gliomas and result in a neo-enzymatic activity that results in reduction of alpha-ketoglutarate to D-2-hydroxyglutarate. alpha-hydroxyglutarate 153-173 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-15 24529257-3 2014 RESULTS: We determined the levels of D-2-hydroxyglutarate in glioma tissues with IDH1 mutations. alpha-hydroxyglutarate 37-57 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 81-85 24529257-6 2014 Enzyme kinetics of mutant IDH protein correlated well with D-2-hydroxyglutarate production in cells with R132H exhibiting the highest and R132L the lowest KM for alpha-ketoglutarate. alpha-hydroxyglutarate 59-79 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 24531386-2 2014 The IDH1 mutations lead to a loss of its normal enzymatic activity and acquisition of neomorphic activity in production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2-HG), which finally cause alterations of multiple gene expression of tumorigenesis-associated alpha-KG-dependent enzymes. alpha-hydroxyglutarate 158-176 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-8 24150401-2 2014 Prooxidant and antiproliferative effects of IDH1 mutations and its D-2-hydroxyglutarate (2-HG) product have been described in vitro, but inconsistently observed. alpha-hydroxyglutarate 67-87 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-48 24344214-0 2014 Serum 2-hydroxyglutarate production in IDH1- and IDH2-mutated de novo acute myeloid leukemia: a study by the Acute Leukemia French Association group. alpha-hydroxyglutarate 6-24 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 39-43 24344214-1 2014 PURPOSE: Mutated isocitrate dehydrogenases (IDHs) 1 and 2 produce high levels of 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 81-99 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 17-57 25485496-3 2014 Mutant IDH acts through a novel mechanism of oncogenesis, producing high levels of the metabolite 2-hydroxyglutarate, which interferes with the function of alpha-ketoglutarate-dependent enzymes that regulate diverse cellular processes including histone demethylation and DNA modification. alpha-hydroxyglutarate 98-116 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 24386123-12 2013 Finally, mutations of IDH1 (IDH1 (R132)) and IDH2 (IDH2 (R172)) leading to production of the TET inhibiting oncometabolite 2-hydroxyglutarate in germ cell cancer cell lines were not detected. alpha-hydroxyglutarate 123-141 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 22-26 24386123-12 2013 Finally, mutations of IDH1 (IDH1 (R132)) and IDH2 (IDH2 (R172)) leading to production of the TET inhibiting oncometabolite 2-hydroxyglutarate in germ cell cancer cell lines were not detected. alpha-hydroxyglutarate 123-141 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 23801081-2 2013 Mutation of R132 of IDH1 abrogates generation of alpha-KG and leads to conversion of alpha-KG to 2-hydroxyglutarate. alpha-hydroxyglutarate 97-115 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 24049096-1 2013 BACKGROUND: Mosaic IDH1 mutations are described as the cause of metaphyseal chondromatosis with increased urinary excretion of D-2-hydroxyglutarate (MC-HGA), and mutations in IDH2 as the cause of D-2-hydroxyglutaric aciduria (D-2HGA) type II. alpha-hydroxyglutarate 127-147 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 19-23 23954893-2 2013 Mutant IDH produces 2-hydroxyglutarate (2HG), which induces histone- and DNA-hypermethylation through inhibition of epigenetic regulators. alpha-hydroxyglutarate 20-38 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 24082129-1 2013 The 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an "oncometabolite." alpha-hydroxyglutarate 4-22 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 110-114 23592268-1 2013 2-Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-104 24077805-1 2013 Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade and progressive gliomas and are characterized by the production of 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate by the mutant enzyme. alpha-hydroxyglutarate 148-166 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-47 24077805-1 2013 Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade and progressive gliomas and are characterized by the production of 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate by the mutant enzyme. alpha-hydroxyglutarate 148-166 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 49-53 24077826-3 2013 These mutations impart the mutant IDH enzyme with a neomorphic activity - the ability to synthesize 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 100-118 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-37 23999439-0 2013 Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate. alpha-hydroxyglutarate 79-97 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-27 23999439-1 2013 The investigation of metabolic pathways disturbed in isocitrate dehydrogenase (IDH) mutant tumors revealed that the hallmark metabolic alteration is the production of D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 167-187 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 79-82 23877318-6 2013 The production of 2-hydroxyglutarate and enhanced NADP+ levels in tumor cells with mutant IDH1/2 suggest mechanisms through which these mutations contribute to tumorigenesis. alpha-hydroxyglutarate 18-36 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 90-94 23731180-0 2013 Mutant IDH1 enhances the production of 2-hydroxyglutarate due to its kinetic mechanism. alpha-hydroxyglutarate 39-57 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 23731180-2 2013 Cancer-associated somatic mutations in IDH1 result in a loss of this normal function but a gain in a new or neomorphic ability to convert alphaKG to the oncometabolite 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 168-186 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 39-43 23847760-2 2013 IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. alpha-hydroxyglutarate 200-220 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 23847760-2 2013 IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. alpha-hydroxyglutarate 200-220 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 23641016-0 2013 Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia. alpha-hydroxyglutarate 6-24 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 40-64 23641016-1 2013 Cancer-associated isocitrate dehydrogenase (IDH) mutations produce the metabolite 2-hydroxyglutarate (2HG), but the clinical utility of 2HG has not been established. alpha-hydroxyglutarate 82-100 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 18-42 23641016-1 2013 Cancer-associated isocitrate dehydrogenase (IDH) mutations produce the metabolite 2-hydroxyglutarate (2HG), but the clinical utility of 2HG has not been established. alpha-hydroxyglutarate 82-100 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-47 23795241-2 2013 Different from the wild-type enzyme, mutant IDH1 catalyzes the reduction of alpha-ketoglutaric acid to D-2-hydroxyglutaric acid. alpha-hydroxyglutarate 103-127 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-48 23795241-5 2013 These compounds exhibit >60-fold selectivity against wild-type IDH1 and can inhibit the production of D-2-hydroxyglutaric acid in IDH1 mutated cells, representing novel chemical probes for cancer biology studies. alpha-hydroxyglutarate 105-129 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 133-137 23541771-2 2013 Mutated IDH1 produces the oncometabolite 2-hydroxyglutarate rather than alpha-ketoglutarate or isocitrate. alpha-hydroxyglutarate 41-59 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 8-12 23410661-1 2013 OBJECTIVES: To determine whether accumulation of 2-hydroxyglutarate in IDH-mutated low-grade gliomas (LGG; WHO grade II) correlates with their malignant transformation and to evaluate changes in metabolite levels during malignant progression. alpha-hydroxyglutarate 49-67 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 71-74 23410661-8 2013 Increased 2-hydroxyglutarate/isocitrate ratios were seen in patients with IDH1-mutated LGG and sGBM, in comparison with those with IDH1-nonmutated LGG, pGBM, and nonglioma groups. alpha-hydroxyglutarate 10-28 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 74-78 23410661-11 2013 CONCLUSION: Although intratumoral 2-hydroxyglutarate accumulation provides a marker for the presence of IDH mutations, the metabolite is not a useful biomarker for identifying malignant transformation or evaluating malignant progression. alpha-hydroxyglutarate 34-52 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 104-107 24252742-5 2013 RESULTS: LC-MS and in situ mass spectrometric imaging by LESA-nano ESI-FTICR revealed high levels of the proposed oncometabolite D-2-hydroxyglutarate (D-2HG), the product of enzymatic conversion of alpha-ketoglutarate (alpha-KG) by IDH1-R132H, in the tumor but not in surrounding brain parenchyma. alpha-hydroxyglutarate 129-149 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 232-236 23905201-0 2010 ML309: A potent inhibitor of R132H mutant IDH1 capable of reducing 2-hydroxyglutarate production in U87 MG glioblastoma cells The emergence of the role of isocitrate dehydrogenase (IDH) in cancer resulted from genomic sequencing for 22 glioma genomes that found recurrent mutation of IDH1 on chromosome 2q33. alpha-hydroxyglutarate 67-85 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-46 23905201-0 2010 ML309: A potent inhibitor of R132H mutant IDH1 capable of reducing 2-hydroxyglutarate production in U87 MG glioblastoma cells The emergence of the role of isocitrate dehydrogenase (IDH) in cancer resulted from genomic sequencing for 22 glioma genomes that found recurrent mutation of IDH1 on chromosome 2q33. alpha-hydroxyglutarate 67-85 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-45 23630074-4 2013 Cancer-associated IDH mutations alter the enzymes such that they reduce 2OG to the structurally similar metabolite (R)-2-hydroxyglutarate [(R)-2HG]. alpha-hydroxyglutarate 115-137 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 18-21 23481705-2 2013 Cells transfected with mutant isocitrate dehydrogenase (IDH) show increased methylation of histone lysine residues, including H3K9me3, because of inhibition of histone demethylases by 2-hydroxyglutarate. alpha-hydroxyglutarate 184-202 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-54 23481705-2 2013 Cells transfected with mutant isocitrate dehydrogenase (IDH) show increased methylation of histone lysine residues, including H3K9me3, because of inhibition of histone demethylases by 2-hydroxyglutarate. alpha-hydroxyglutarate 184-202 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 56-59 23393090-1 2013 Mutations in IDH1 and IDH2, the genes coding for isocitrate dehydrogenases 1 and 2, are common in several human cancers, including leukemias, and result in overproduction of the (R)-enantiomer of 2-hydroxyglutarate [(R)-2HG]. alpha-hydroxyglutarate 196-214 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 23432648-6 2013 Mutant IDH1 results in the production of a metabolite 2-hydroxyglutarate (2-HG) that can inhibit DNA and histone demethylating enzymes resulting in the glioma-CpG island phenotype (G-CIMP) and increased histone methylation marks. alpha-hydroxyglutarate 54-72 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 23432648-6 2013 Mutant IDH1 results in the production of a metabolite 2-hydroxyglutarate (2-HG) that can inhibit DNA and histone demethylating enzymes resulting in the glioma-CpG island phenotype (G-CIMP) and increased histone methylation marks. alpha-hydroxyglutarate 74-78 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 23264629-1 2013 Monoallelic point mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) and its mitochondrial homolog IDH2 can lead to elevated levels of 2-hydroxyglutarate (2HG) in multiple cancers. alpha-hydroxyglutarate 141-159 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 41-67 23264629-1 2013 Monoallelic point mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) and its mitochondrial homolog IDH2 can lead to elevated levels of 2-hydroxyglutarate (2HG) in multiple cancers. alpha-hydroxyglutarate 141-159 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 69-73 22680765-0 2013 2-Hydroxyglutarate in IDH mutant acute myeloid leukemia: predicting patient responses, minimal residual disease and correlations with methylcytosine and hydroxymethylcytosine levels. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 22-25 23373447-4 2013 Rapidly emerging work on the consequences of mutant IDH1 protein expression suggests that its neomorphic enzymatic activity catalyzing the production of the oncometabolite 2-hydroxyglutarate influences a range of cellular programs that affect the epigenome, transcriptional programs, hypoxia-inducible factor biology, and development. alpha-hydroxyglutarate 172-190 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 52-56 22391558-2 2013 The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of alpha-KG, linking 5mC oxidation to cancer development. alpha-hydroxyglutarate 162-180 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 118-122 23204232-0 2013 Disruption of wild-type IDH1 suppresses D-2-hydroxyglutarate production in IDH1-mutated gliomas. alpha-hydroxyglutarate 40-60 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-28 23204232-0 2013 Disruption of wild-type IDH1 suppresses D-2-hydroxyglutarate production in IDH1-mutated gliomas. alpha-hydroxyglutarate 40-60 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 75-79 23204232-1 2013 Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 190-210 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 63-89 23204232-1 2013 Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 190-210 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 91-95 23232569-2 2013 Mutant IDH enzyme loses its normal activity to convert isocitrate into alpha-ketoglutarate (alphaKG) and instead acquires the ability to reduce alphaKG to D-2-hydroxyglutarate. alpha-hydroxyglutarate 155-175 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 23232569-3 2013 Through direct competition with alphaKG, accumulation of the oncometabolite D-2-hydroxyglutarate in IDH mutated tumors results in inhibition of alphaKG-dependent dioxygenases involved in DNA and histone demethylation. alpha-hydroxyglutarate 76-96 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 100-103 23863747-3 2013 Here we show that the IDH variants in CS are also associated with a hypermethylation phenotype and display increased production of the oncometabolite 2-hydroxyglutarate, supporting the role of mutant IDH-produced 2-hydroxyglutarate as an inhibitor of TET-mediated DNA demethylation. alpha-hydroxyglutarate 150-168 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 22-25 23863747-3 2013 Here we show that the IDH variants in CS are also associated with a hypermethylation phenotype and display increased production of the oncometabolite 2-hydroxyglutarate, supporting the role of mutant IDH-produced 2-hydroxyglutarate as an inhibitor of TET-mediated DNA demethylation. alpha-hydroxyglutarate 213-231 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 22-25 23863747-3 2013 Here we show that the IDH variants in CS are also associated with a hypermethylation phenotype and display increased production of the oncometabolite 2-hydroxyglutarate, supporting the role of mutant IDH-produced 2-hydroxyglutarate as an inhibitor of TET-mediated DNA demethylation. alpha-hydroxyglutarate 213-231 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 200-203 24077277-1 2013 Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to alpha-ketoglutarate (alpha-KG) and acquires new activity whereby it converts alpha-KG to 2-hydroxyglutarate. alpha-hydroxyglutarate 230-248 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-36 24077277-1 2013 Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to alpha-ketoglutarate (alpha-KG) and acquires new activity whereby it converts alpha-KG to 2-hydroxyglutarate. alpha-hydroxyglutarate 230-248 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-42 23507484-3 2013 In addition, IDH1/2 mutations confer a gain-of-function, allowing the enzymes to process alpha-ketoglutarate to 2-hydroxyglutarate, which inhibits the TET proteins and ultimately induces the same hypermethylation phenotype. alpha-hydroxyglutarate 112-130 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-19 23038259-1 2012 Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 165-183 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-56 23038259-1 2012 Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 165-183 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-72 23117877-1 2012 Levels of (D)-2-hydroxyglutarate [D2HG, (R)-2-hydroxyglutarate] are increased in some metabolic diseases and in neoplasms with mutations in the isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) genes. alpha-hydroxyglutarate 10-32 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 172-176 23117877-1 2012 Levels of (D)-2-hydroxyglutarate [D2HG, (R)-2-hydroxyglutarate] are increased in some metabolic diseases and in neoplasms with mutations in the isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) genes. alpha-hydroxyglutarate 40-62 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 172-176 23090985-1 2012 The arginine 132 (R132) mutation of isocitrate dehydrogenase -1 (IDH1(R132)) results in production of 2-hydroxyglutarate (2-HG) and is associated with a better prognosis compared with wild-type (WT) in glioma patients. alpha-hydroxyglutarate 102-120 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 65-69 23074281-2 2012 Serum and myeloblast samples from patients with IDH-mutant AML contain high levels of the metabolite 2-hydroxyglutarate (2-HG), a product of the altered IDH protein. alpha-hydroxyglutarate 101-119 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 48-51 23074281-2 2012 Serum and myeloblast samples from patients with IDH-mutant AML contain high levels of the metabolite 2-hydroxyglutarate (2-HG), a product of the altered IDH protein. alpha-hydroxyglutarate 101-119 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 153-156 23071358-2 2012 Mutations targeting IDH1 and IDH2 result in simultaneous loss of their normal catalytic activity, the production of alpha-ketoglutarate (alpha-KG), and gain of a new function, the production of 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 194-212 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 22426639-0 2012 Detection of "oncometabolite" 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma. alpha-hydroxyglutarate 30-48 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 98-104 22426639-1 2012 Somatic mutations in isocitrate dehydrogenase (IDH)1 and 2 have been identified in a subset of gliomas, rendering these tumors with elevated levels of "oncometabolite," D-2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 169-189 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-58 21913188-2 2012 Mutated IDH1 or IDH2 protein leads to the generation of excessive amounts of the metabolite 2-hydroxyglutarate (2HG) in tumor cells. alpha-hydroxyglutarate 92-110 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 8-12 22683334-0 2012 IDH1 and IDH2 have critical roles in 2-hydroxyglutarate production in D-2-hydroxyglutarate dehydrogenase depleted cells. alpha-hydroxyglutarate 37-55 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 22399191-7 2012 The mutated IDH1/2 enzyme generates D-2-hydroxyglutarate. alpha-hydroxyglutarate 36-56 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-18 22105553-3 2012 Mutations of IDH1 and IDH2 led to simultaneous loss and gain of activities in the production of alpha-ketoglutarate and 2-hydroxyglutarate, respectively. alpha-hydroxyglutarate 120-138 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 22015945-0 2012 Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. alpha-hydroxyglutarate 26-44 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 70-74 22343901-1 2012 Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 have been identified in gliomas, acute myeloid leukaemias (AML) and chondrosarcomas, and share a novel enzymatic property of producing 2-hydroxyglutarate (2HG) from alpha-ketoglutarate. alpha-hydroxyglutarate 201-219 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-49 22343901-1 2012 Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 have been identified in gliomas, acute myeloid leukaemias (AML) and chondrosarcomas, and share a novel enzymatic property of producing 2-hydroxyglutarate (2HG) from alpha-ketoglutarate. alpha-hydroxyglutarate 201-219 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 51-55 22281806-0 2012 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 67-70 22238331-1 2012 2-Hydroxyglutarate (2-HG) is a potential oncometabolite involved in gliomagenesis that has been identified as an aberrant product of isocitrate dehydrogenase (IDH)-mutated glial tumors. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 133-157 22238331-1 2012 2-Hydroxyglutarate (2-HG) is a potential oncometabolite involved in gliomagenesis that has been identified as an aberrant product of isocitrate dehydrogenase (IDH)-mutated glial tumors. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 159-162 22238331-1 2012 2-Hydroxyglutarate (2-HG) is a potential oncometabolite involved in gliomagenesis that has been identified as an aberrant product of isocitrate dehydrogenase (IDH)-mutated glial tumors. alpha-hydroxyglutarate 20-24 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 133-157 22238331-1 2012 2-Hydroxyglutarate (2-HG) is a potential oncometabolite involved in gliomagenesis that has been identified as an aberrant product of isocitrate dehydrogenase (IDH)-mutated glial tumors. alpha-hydroxyglutarate 20-24 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 159-162 22238332-0 2012 Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy. alpha-hydroxyglutarate 13-31 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-38 22238332-2 2012 Arginine 132 (R132) mutations in the enzyme IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. alpha-hydroxyglutarate 95-113 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-48 22238333-0 2012 Magnetic resonance of 2-hydroxyglutarate in IDH1-mutated low-grade gliomas. alpha-hydroxyglutarate 22-40 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-48 22238333-2 2012 IDH1/2 mutations result in aberrant enzymatic production of the potential oncometabolite D-2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 89-109 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 22675360-8 2012 Arg172 mutants of human IDH2-frequently found with similar mutants of cytosolic IDH1 in grade 2 and 3 gliomas, secondary glioblastomas, and acute myeloid leukemia-catalyze reductive carboxylation of 2-oxoglutarate and reduction to D-2-hydroxyglutarate, which strengthens the neoplastic phenotype by competitive inhibition of histone demethylation and 5-methylcytosine hydroxylation, leading to genome-wide histone and DNA methylation alternations. alpha-hydroxyglutarate 231-251 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 80-84 22180306-8 2012 In an analysis of frozen tissue specimens, IDH1 mutation was associated with highly elevated tissue levels of the enzymatic product 2-hydroxyglutarate. alpha-hydroxyglutarate 132-150 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 43-47 22106302-7 2011 The increased IDH2-dependent carboxylation of glutamine-derived alpha-ketoglutarate in hypoxia is associated with a concomitant increased synthesis of 2-hydroxyglutarate (2HG) in cells with wild-type IDH1 and IDH2. alpha-hydroxyglutarate 151-169 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 200-204 22002076-3 2011 IDH mutations cause loss of native enzymatic activities and confer novel activity of converting alpha-KG to 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 108-126 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 21889589-2 2011 Overexpression studies with IDH1(R132H) and IDH2(R172K) mutations demonstrated that the enzymes acquired a new function, converting 2-ketoglutarate (2-KG) to d-2-hydroxyglutarate (D-2-HG), in lieu of the normal IDH reaction which reversibly converts isocitrate to 2-KG. alpha-hydroxyglutarate 158-178 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 21889589-2 2011 Overexpression studies with IDH1(R132H) and IDH2(R172K) mutations demonstrated that the enzymes acquired a new function, converting 2-ketoglutarate (2-KG) to d-2-hydroxyglutarate (D-2-HG), in lieu of the normal IDH reaction which reversibly converts isocitrate to 2-KG. alpha-hydroxyglutarate 180-186 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 21939466-5 2011 Specifically, 2-hydroxyglutarate, the oncometabolite produced by mutant IDH1 and IDH2 proteins, has been shown to function as a competitive inhibitor of various alpha-ketoglutarate (alpha-KG)-dependent dioxygenases, including histone demethylases and members of the ten-eleven-translocation (TET) family of 5-methylcytosine (5mC) hydroxylases. alpha-hydroxyglutarate 14-32 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 72-76 21885076-7 2011 IDH1/IDH2 mutation results in a new enzymatic activity transforming alpha-ketoglutarate into 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 93-111 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 21885076-7 2011 IDH1/IDH2 mutation results in a new enzymatic activity transforming alpha-ketoglutarate into 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 113-117 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 21294161-4 2011 The oncogenic pathway triggered by IDH mutations may involve the activation of hypoxia-inducible factor pathway as well as the acquisition of a novel (gain of enzymatic) function consuming NADPH and generating alpha-hydroxyglutarate. alpha-hydroxyglutarate 210-232 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-38 21641335-4 2011 IDH1 and IDH2 mutations lead to simultaneous loss and gain of activities in the production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2HG), respectively, and result in lowering NADPH levels even further. alpha-hydroxyglutarate 129-147 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 21598255-6 2011 Heterozygous somatic IDH1/IDH2 mutations, which result in the production of a potential oncometabolite, 2-hydroxyglutarate, were only detected in central and periosteal cartilaginous tumours, and were found in at least 56% of these, ~40% of which were represented by R132C. alpha-hydroxyglutarate 104-122 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-25 21554053-4 2011 The consequences of IDH1/IDH2 mutation (that results in a new enzymatic activity transforming alphacetoglutarate into 2-hydroxyglutarate) are currently under investigation. alpha-hydroxyglutarate 118-136 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 21284999-3 2011 Based on the findings that glioma-derived mutations in IDH1 can inhibit the catalytic activity of the enzyme, induce HIF-1alpha, and can produce 2-hydroxyglutarate, two research groups speculated that the IDH mutations may contribute to the promotion of tumorigenesis in gliomas. alpha-hydroxyglutarate 145-163 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 55-59 21284999-3 2011 Based on the findings that glioma-derived mutations in IDH1 can inhibit the catalytic activity of the enzyme, induce HIF-1alpha, and can produce 2-hydroxyglutarate, two research groups speculated that the IDH mutations may contribute to the promotion of tumorigenesis in gliomas. alpha-hydroxyglutarate 145-163 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 55-58 21080253-1 2011 Elevated levels of D: -2-hydroxyglutarate (D: -2-HG) occur in gliomas and myeloid leukemias associated with mutations of IDH1 and IDH2. alpha-hydroxyglutarate 19-41 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 121-125 21225914-2 2011 Elevated levels of D-2-hydroxyglutarate have been demonstrated with malignant gliomas and myeloid leukemias associated with somatic mutations of the genes encoding NADP(+)-dependent isocitrate dehydrogenases (IDH1 and IDH2, respectively). alpha-hydroxyglutarate 19-39 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 209-213 21289278-2 2011 When mutated, IDH1 and IDH2 gain the ability to produce the metabolite (R)-2-hydroxyglutarate (2HG), but the downstream effects of mutant IDH1 and IDH2 proteins or of 2HG on cellular metabolism are unknown. alpha-hydroxyglutarate 71-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-18 21251613-1 2011 IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2-HG), respectively. alpha-hydroxyglutarate 188-206 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 22089927-8 2011 Members of this superfamily can be inhibited by endogenous metabolites, including fumarate and succinate, which accumulate in tumors that have fumarate hydratase (FH) or succinate dehydrogenase (SDH) mutations, respectively, as well as by the 2-hydroxyglutarate detected in isocitrate dehydrogenase (IDH) mutant tumors. alpha-hydroxyglutarate 243-261 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 274-298 22089927-8 2011 Members of this superfamily can be inhibited by endogenous metabolites, including fumarate and succinate, which accumulate in tumors that have fumarate hydratase (FH) or succinate dehydrogenase (SDH) mutations, respectively, as well as by the 2-hydroxyglutarate detected in isocitrate dehydrogenase (IDH) mutant tumors. alpha-hydroxyglutarate 243-261 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 300-303 20615753-8 2011 Mutated IDH1 has an altered catalytic activity that results in the accumulation of 2-hydroxyglutarate. alpha-hydroxyglutarate 83-101 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 8-12 21625441-5 2011 IDH1 and IDH2 mutations cause both loss of normal enzyme function and gain-of-function, causing reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG) which accumulates. alpha-hydroxyglutarate 121-141 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 21130701-1 2010 Cancer-associated IDH mutations are characterized by neomorphic enzyme activity and resultant 2-hydroxyglutarate (2HG) production. alpha-hydroxyglutarate 94-112 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 18-21 20972461-3 2010 Soon, it became clear that the mutations identified impaired the ability of IDH1 and IDH2 to catalyze the conversion of isocitrate to alpha-ketoglutarate (alphaKG), whereas conferring a gain of a novel enzymatic activity leading to the reduction of alphaKG to the metabolite D2-hydroxyglutarate (D-2HG). alpha-hydroxyglutarate 275-294 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 76-80 21045145-1 2010 Mutation at the R132 residue of isocitrate dehydrogenase 1 (IDH1), frequently found in gliomas and acute myelogenous leukemia, creates a neoenzyme that produces 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate (alpha-KG). alpha-hydroxyglutarate 161-179 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-58 21045145-1 2010 Mutation at the R132 residue of isocitrate dehydrogenase 1 (IDH1), frequently found in gliomas and acute myelogenous leukemia, creates a neoenzyme that produces 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate (alpha-KG). alpha-hydroxyglutarate 161-179 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 60-64 20975740-3 2010 This mutation impairs the oxidative IDH activity of the enzyme, but renders a new reduction function of converting alpha-ketoglutarate (alphaKG) to 2-hydroxyglutarate. alpha-hydroxyglutarate 148-166 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 36-39 20659156-0 2010 Increased levels of 2-hydroxyglutarate in AML patients with IDH1-R132H and IDH2-R140Q mutations. alpha-hydroxyglutarate 20-38 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 60-64 20962328-1 2010 Recurrent somatic mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes that result in the accumulation of D-2-hydroxyglutarate (D-2-HG) have been identified in malignant gliomas and in acute myeloid leukemia (AML). alpha-hydroxyglutarate 119-139 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-61 20962328-1 2010 Recurrent somatic mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes that result in the accumulation of D-2-hydroxyglutarate (D-2-HG) have been identified in malignant gliomas and in acute myeloid leukemia (AML). alpha-hydroxyglutarate 119-139 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 63-67 20692206-3 2010 The heterozygous somatic mutations at arginine R132 (IDH1) and at R140 or R172 (IDH2) in the enzyme active site confer a gain of function to the enzymes, which can both produce the metabolite 2-hydroxyglutarate. alpha-hydroxyglutarate 192-210 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 53-57 20513808-8 2010 IDH1 and IDH2 mutations are usually heterozygous in cancer, and they appear to confer a neomorphic enzyme activity for the enzymes to catalyze the production of D-2-hydroxyglutarate. alpha-hydroxyglutarate 161-181 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 20559394-0 2010 Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. alpha-hydroxyglutarate 41-59 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 18-22 20127344-4 2010 Mutated IDH1 has a gain of function to produce 2-hydroxyglutarate by NADPH-dependent reduction of alpha-ketoglutarate, but it is unknown whether NADPH production in gliomas is affected by IDH1 mutations. alpha-hydroxyglutarate 47-65 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 8-12 20367200-0 2010 2-hydroxyglutarate accumulation caused by IDH mutation is involved in the formation of malignant gliomas. alpha-hydroxyglutarate 0-18 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-45 20305482-0 2010 IDH1 and IDH2 mutations in gliomas and the associated induction of hypoxia-inducible factor and production of 2-hydroxyglutarate. alpha-hydroxyglutarate 110-128 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 20171147-0 2010 The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. alpha-hydroxyglutarate 132-150 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-46 20171147-1 2010 The somatic mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) observed in gliomas can lead to the production of 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 119-137 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-61 20171147-1 2010 The somatic mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) observed in gliomas can lead to the production of 2-hydroxyglutarate (2HG). alpha-hydroxyglutarate 119-137 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 63-67 20142433-4 2010 A glioma study revealed that IDH1 mutations cause a gain-of-function, resulting in the production and accumulation of 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 118-136 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 29-33 20129244-3 2010 identified 2-hydroxyglutarate as a product of tumor-associated IDH mutants with potential oncogenic activities. alpha-hydroxyglutarate 11-29 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 63-66 19935646-0 2009 Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. alpha-hydroxyglutarate 41-59 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 18-22 33811494-0 2021 The role of 2-hydroxyglutarate magnetic resonance spectroscopy for the determination of isocitrate dehydrogenase status in lower grade gliomas versus glioblastoma: a systematic review and meta-analysis of diagnostic test accuracy. alpha-hydroxyglutarate 12-30 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 88-112 33811494-2 2021 Determination of 2-hydroxyglutarate (2-HG) presence through MRS is a means of determining IDH status; however, differences may be seen by grade. alpha-hydroxyglutarate 17-35 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 90-93 33811494-2 2021 Determination of 2-hydroxyglutarate (2-HG) presence through MRS is a means of determining IDH status; however, differences may be seen by grade. alpha-hydroxyglutarate 37-41 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 90-93 33808599-4 2021 This is the case of IDH1/2 mutations generating the abnormal conversion of alpha-ketoglutarate (KG) to 2-hydroxyglutarate, an oncometabolite inhibiting KG-dependent enzymes, such as the TET family of genes (pivotal in characterizing leukemia cells either by mutations, e.g., TET2, or by altered expression, e.g., TET1/2/3). alpha-hydroxyglutarate 103-121 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-26 30170631-8 2018 Moreover, patients with IDH-mutant gliomas demonstrated higher levels of D-2-hydroxyglutarate in the CSF, in comparison to patients with other tumor types, or controls. alpha-hydroxyglutarate 73-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 24-27 34609036-0 2022 Improving D-2-hydroxyglutarate MR spectroscopic imaging in mutant isocitrate dehydrogenase glioma patients with multiplexed RF-receive/B0 -shim array coils at 3 T. MR spectroscopic imaging (MRSI) noninvasively maps the metabolism of human brains. alpha-hydroxyglutarate 10-30 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-90 34609036-1 2022 In particular, the imaging of D-2-hydroxyglutarate (2HG) produced by glioma isocitrate dehydrogenase (IDH) mutations has become a key application in neuro-oncology. alpha-hydroxyglutarate 30-50 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 102-105 34941573-1 2022 The discovery of the oncometabolite 2-hydroxyglutarate in isocitrate dehydrogenase (IDH)1-mutated tumor entities affirmed the role of metabolism in cancer. alpha-hydroxyglutarate 36-54 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 84-89 34224582-0 2021 Absolute Quantification of 2-Hydroxyglutarate on Tissue by MALDI MSI for Rapid and Precise Identification of IDH Mutations in Human Glioma. alpha-hydroxyglutarate 27-45 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 109-112 34224582-2 2021 Herein, we presented a method using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) for absolute quantification of 2-hydroxyglutarate (2-HG) on tissues to identify IDH mutations and evaluate tumour residue. alpha-hydroxyglutarate 149-167 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 198-201 34224582-2 2021 Herein, we presented a method using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) for absolute quantification of 2-hydroxyglutarate (2-HG) on tissues to identify IDH mutations and evaluate tumour residue. alpha-hydroxyglutarate 169-173 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 198-201 34224582-4 2021 The cut-off value of 2-HG was set as 0.81 pmol/mug to identify IDH mutant (IDHmt) gliomas with 100% specificity and sensitivity. alpha-hydroxyglutarate 21-25 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 63-66 34535560-2 2021 Recent work discovered that the oncometabolite 2-hydroxyglutarate (2-HG), produced by neomorphic isocitrate dehydrogenase 1/2 (IDH1/2) mutations, confers a homology directed repair (HDR) defect through 2-HG-induced histone hypermethylation masking HDR signaling. alpha-hydroxyglutarate 47-65 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 127-133 34535560-2 2021 Recent work discovered that the oncometabolite 2-hydroxyglutarate (2-HG), produced by neomorphic isocitrate dehydrogenase 1/2 (IDH1/2) mutations, confers a homology directed repair (HDR) defect through 2-HG-induced histone hypermethylation masking HDR signaling. alpha-hydroxyglutarate 67-71 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 127-133 34535560-2 2021 Recent work discovered that the oncometabolite 2-hydroxyglutarate (2-HG), produced by neomorphic isocitrate dehydrogenase 1/2 (IDH1/2) mutations, confers a homology directed repair (HDR) defect through 2-HG-induced histone hypermethylation masking HDR signaling. alpha-hydroxyglutarate 202-206 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 127-133 34610989-2 2021 IDH1/2 mutations are thought to be associated with seizures owing to the structural similarity between D2HG and glutamate. alpha-hydroxyglutarate 103-107 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 34610989-12 2021 Increased preoperative seizure risk was only observed in tumors with 2HG concentration above the cutoff value among IDH-Mut (IDH-Mut with above the cutoff value: 71.4 % vs IDH-Mut with below the cutoff value: 28.6 %, p = 0.031). alpha-hydroxyglutarate 69-72 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 125-128 34610989-12 2021 Increased preoperative seizure risk was only observed in tumors with 2HG concentration above the cutoff value among IDH-Mut (IDH-Mut with above the cutoff value: 71.4 % vs IDH-Mut with below the cutoff value: 28.6 %, p = 0.031). alpha-hydroxyglutarate 69-72 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 172-175 34610989-13 2021 Multivariate analysis, including IDH1/2 mutation status, tissue 2HG concentration, WHO grade and 1p/19q codeletion, revealed that only increased tissue 2HG concentration was associated with preoperative seizures (odds ratio 5.86, 95% confidence interval 1.02-48.5, p = 0.048).ConclusionsWe showed that high tissue 2HG concentration was associated with preoperative seizures, suggesting that excess 2HG increases risk of preoperative seizures in IDH1/2 mutant tumors. alpha-hydroxyglutarate 398-401 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 445-451 34829476-0 2021 Detection of 2-Hydroxyglutarate by 3.0-Tesla Magnetic Resonance Spectroscopy in Gliomas with Rare IDH Mutations: Making Sense of "False-Positive" Cases. alpha-hydroxyglutarate 13-31 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 98-101 34725432-1 2021 Cancer linked isocitrate dehydrogenase (IDH) 1 variants, notably R132H IDH1, manifest a "gain-of-function" to reduce 2-oxoglutarate to 2-hydroxyglutarate. alpha-hydroxyglutarate 135-153 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 71-75 34321251-1 2021 Point mutations in isocitrate dehydrogenase 1 (IDH1) result in conversion of alpha-ketoglutarate to the oncometabolite, D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 120-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 19-45 34321251-1 2021 Point mutations in isocitrate dehydrogenase 1 (IDH1) result in conversion of alpha-ketoglutarate to the oncometabolite, D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 120-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-51 34321251-1 2021 Point mutations in isocitrate dehydrogenase 1 (IDH1) result in conversion of alpha-ketoglutarate to the oncometabolite, D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 142-146 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 19-45 34321251-1 2021 Point mutations in isocitrate dehydrogenase 1 (IDH1) result in conversion of alpha-ketoglutarate to the oncometabolite, D-2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 142-146 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-51 34289383-1 2021 Mutant isocitrate dehydrogenase (IDH) 1 and 2 play a pathogenic role in cancers, including acute myeloid leukemia (AML), by producing oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 149-167 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-45 34289383-1 2021 Mutant isocitrate dehydrogenase (IDH) 1 and 2 play a pathogenic role in cancers, including acute myeloid leukemia (AML), by producing oncometabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 169-173 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-45 34531086-1 2021 BACKGROUND: Mutant isocitrate dehydrogenase (IDH) in chondrosarcoma produces the oncometabolite 2-hydroxyglutarate (2-HG) and contributes to malignant progression, and is therefore a potential therapeutic target for chondrosarcoma. alpha-hydroxyglutarate 96-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 19-43 34531086-1 2021 BACKGROUND: Mutant isocitrate dehydrogenase (IDH) in chondrosarcoma produces the oncometabolite 2-hydroxyglutarate (2-HG) and contributes to malignant progression, and is therefore a potential therapeutic target for chondrosarcoma. alpha-hydroxyglutarate 96-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 45-48 34531086-1 2021 BACKGROUND: Mutant isocitrate dehydrogenase (IDH) in chondrosarcoma produces the oncometabolite 2-hydroxyglutarate (2-HG) and contributes to malignant progression, and is therefore a potential therapeutic target for chondrosarcoma. alpha-hydroxyglutarate 116-120 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 19-43 34531086-1 2021 BACKGROUND: Mutant isocitrate dehydrogenase (IDH) in chondrosarcoma produces the oncometabolite 2-hydroxyglutarate (2-HG) and contributes to malignant progression, and is therefore a potential therapeutic target for chondrosarcoma. alpha-hydroxyglutarate 116-120 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 45-48 34516556-1 2021 Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations and their key effector 2-hydroxyglutarate (2-HG) have been reported to promote oncogenesis in various human cancers. alpha-hydroxyglutarate 75-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-40 34516556-1 2021 Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations and their key effector 2-hydroxyglutarate (2-HG) have been reported to promote oncogenesis in various human cancers. alpha-hydroxyglutarate 95-99 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-40 34516556-3 2021 We found that IDH1/2 mutants induced intracellular 2-HG accumulation and inhibited cell proliferation. alpha-hydroxyglutarate 51-55 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-20 34571995-1 2021 Isocitrate dehydrogenase (IDH) mutations are common genetic abnormalities in glioma, which result in the accumulation of an "oncometabolite", D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 164-170 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 34571995-1 2021 Isocitrate dehydrogenase (IDH) mutations are common genetic abnormalities in glioma, which result in the accumulation of an "oncometabolite", D-2-hydroxyglutarate (D-2-HG). alpha-hydroxyglutarate 164-170 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 34571995-3 2021 Recent studies have revealed that D-2-HG affects DNA/histone methylation, hypoxia signaling, DNA repair, and redox homeostasis, which impacts the oncogenesis of IDH-mutated cancers. alpha-hydroxyglutarate 34-40 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 161-164 34557149-1 2021 The onco-metabolite 2-hydroxyglutarate (2HG), a biomarker of IDH-mutant gliomas, can be detected with 1H MR spectroscopy (1H-MRS). alpha-hydroxyglutarate 20-38 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 61-64 34632051-1 2021 Isocitrate dehydrogenase (IDH) mutations increase (R)-2-hydroxyglutarate (R-2HG) production; however, functional mechanisms of R-2HG in regulating cholangiocarcinoma (CCA) development remain to be further investigated. alpha-hydroxyglutarate 50-72 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 34632051-1 2021 Isocitrate dehydrogenase (IDH) mutations increase (R)-2-hydroxyglutarate (R-2HG) production; however, functional mechanisms of R-2HG in regulating cholangiocarcinoma (CCA) development remain to be further investigated. alpha-hydroxyglutarate 50-72 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 34170697-2 2021 Efficient coupling to localized NADP(H) enables IDH activity to be energized, controlled, and monitored in real time, leading directly to a thermodynamic redox landscape for accumulation of the oncometabolite, 2-hydroxyglutarate, that would occur in biological environments when the R132H variant is present. alpha-hydroxyglutarate 210-228 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 48-51 34095989-3 2021 IDH mutations induce a neomorphic enzyme that converts alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate, which leads to widespread effects on cellular epigenetics and metabolism. alpha-hydroxyglutarate 97-117 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 34095989-5 2021 Targeting D-2-hydroxyglutarate is considered a novel attractive therapeutic approach for low-grade gliomas and the insights from clinical trials suggest that mutant-selective IDH inhibitors are the ideal candidates, with a favorable benefit/risk ratio. alpha-hydroxyglutarate 10-30 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 175-178 34069550-2 2021 These solid IDH1-mutated tumors produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are more vulnerable to disruption of their metabolism. alpha-hydroxyglutarate 59-79 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-16 34069550-2 2021 These solid IDH1-mutated tumors produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are more vulnerable to disruption of their metabolism. alpha-hydroxyglutarate 81-86 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-16 34065652-2 2021 IDH1 mutations, primarily R132H, drive > 80% of low-grade gliomas and secondary glioblastomas and facilitate the NADPH-dependent reduction of alphaKG to the oncometabolite D-2-hydroxyglutarate (D2HG). alpha-hydroxyglutarate 172-192 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 34065652-2 2021 IDH1 mutations, primarily R132H, drive > 80% of low-grade gliomas and secondary glioblastomas and facilitate the NADPH-dependent reduction of alphaKG to the oncometabolite D-2-hydroxyglutarate (D2HG). alpha-hydroxyglutarate 194-198 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 35314408-2 2022 IDH mutation induces accumulation of the onco-metabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 57-75 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 35314408-2 2022 IDH mutation induces accumulation of the onco-metabolite 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 77-81 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 35606087-3 2022 However, accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) in IDH-mutated gliomas leads to suppression of inflammatory pathways in the tumor microenvironment, thereby contributing to the "cold" tumor phenotype. alpha-hydroxyglutarate 44-64 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 76-79 35606087-3 2022 However, accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) in IDH-mutated gliomas leads to suppression of inflammatory pathways in the tumor microenvironment, thereby contributing to the "cold" tumor phenotype. alpha-hydroxyglutarate 66-71 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 76-79 35493690-2 2022 Approximately half of chondrosarcomas harbor gain-of-function mutations in isocitrate dehydrogenase (IDH), and mutant IDH produces 2-hydroxyglutarate (2-HG), which is an oncometabolite that contributes to malignant transformation. alpha-hydroxyglutarate 131-149 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 118-121 35493690-2 2022 Approximately half of chondrosarcomas harbor gain-of-function mutations in isocitrate dehydrogenase (IDH), and mutant IDH produces 2-hydroxyglutarate (2-HG), which is an oncometabolite that contributes to malignant transformation. alpha-hydroxyglutarate 151-155 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 118-121 35493690-4 2022 2-HG is also expected to be a useful biomarker for the diagnosis and treatment of IDH-mutant tumors. alpha-hydroxyglutarate 0-4 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 82-85 35493690-6 2022 Non-invasive monitoring of 2-HG levels is useful to infer that mutant IDH inhibitors reach therapeutic targets and to confirm their therapeutic efficacy in clinical practice. alpha-hydroxyglutarate 27-31 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 70-73 35493690-9 2022 Results: Both intratumoral and serum 2-HG levels were significantly elevated in IDH-mutant tumors, and these levels correlated with decreased survival. alpha-hydroxyglutarate 37-41 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 80-83 35493690-10 2022 Furthermore, we detected intratumoral 2-HG peaks using MR spectroscopy in a xenograft model of IDH-mutant chondrosarcoma, and observed that 2-HG peak signals disappeared after administering an inhibitor of mutant IDH1. alpha-hydroxyglutarate 38-42 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 95-98 35493690-10 2022 Furthermore, we detected intratumoral 2-HG peaks using MR spectroscopy in a xenograft model of IDH-mutant chondrosarcoma, and observed that 2-HG peak signals disappeared after administering an inhibitor of mutant IDH1. alpha-hydroxyglutarate 38-42 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 213-217 35493690-10 2022 Furthermore, we detected intratumoral 2-HG peaks using MR spectroscopy in a xenograft model of IDH-mutant chondrosarcoma, and observed that 2-HG peak signals disappeared after administering an inhibitor of mutant IDH1. alpha-hydroxyglutarate 140-144 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 95-98 35493690-10 2022 Furthermore, we detected intratumoral 2-HG peaks using MR spectroscopy in a xenograft model of IDH-mutant chondrosarcoma, and observed that 2-HG peak signals disappeared after administering an inhibitor of mutant IDH1. alpha-hydroxyglutarate 140-144 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 213-217 35493690-11 2022 Conclusions: Our findings suggest that both intratumoral and serum 2-HG levels represent potentially useful biomarkers for IDH-mutant tumors and that the 2-HG signal in MR spectra has potential value as a non-invasive biomarker. alpha-hydroxyglutarate 67-71 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 123-126 35353219-1 2022 PURPOSE: Isocitrate dehydrogenase enzyme 1 (IDH1) mutations at 132nd amino acid residue (R132*) result in the cellular accumulation of the oncometabolite, 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 155-173 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 9-42 35353219-1 2022 PURPOSE: Isocitrate dehydrogenase enzyme 1 (IDH1) mutations at 132nd amino acid residue (R132*) result in the cellular accumulation of the oncometabolite, 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 155-173 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-48 35353219-1 2022 PURPOSE: Isocitrate dehydrogenase enzyme 1 (IDH1) mutations at 132nd amino acid residue (R132*) result in the cellular accumulation of the oncometabolite, 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 175-179 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 9-42 35353219-1 2022 PURPOSE: Isocitrate dehydrogenase enzyme 1 (IDH1) mutations at 132nd amino acid residue (R132*) result in the cellular accumulation of the oncometabolite, 2-hydroxyglutarate (2-HG). alpha-hydroxyglutarate 175-179 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-48 35267433-2 2022 IDH-mutated genes encode for a neomorphic enzyme that converts alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (2-HG), which accumulates to high concentrations and alters cellular epigenetics and metabolism. alpha-hydroxyglutarate 105-125 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 35267433-2 2022 IDH-mutated genes encode for a neomorphic enzyme that converts alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (2-HG), which accumulates to high concentrations and alters cellular epigenetics and metabolism. alpha-hydroxyglutarate 127-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 35267433-4 2022 Two distinct strategies have been proposed so far and are under intense clinical investigation: (i) reducing the amount of intratumoral 2-HG by directly blocking the function of mutant IDH enzyme; (ii) exploiting the selective epigenetic and metabolic cellular vulnerabilities as a consequence of 2-HG accumulation. alpha-hydroxyglutarate 136-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 185-188 35267433-4 2022 Two distinct strategies have been proposed so far and are under intense clinical investigation: (i) reducing the amount of intratumoral 2-HG by directly blocking the function of mutant IDH enzyme; (ii) exploiting the selective epigenetic and metabolic cellular vulnerabilities as a consequence of 2-HG accumulation. alpha-hydroxyglutarate 297-301 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 185-188 35157758-6 2022 IDH-mutated subtypes, expressing 2-hydroxyglutaric acid, were clearly distinguished from IDH-wildtype subtypes. alpha-hydroxyglutarate 33-55 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 34985589-1 2022 OBJECTIVE: Oncometabolite D-2-hydroxyglutarate (2HG) is pooled in isocitrate dehydrogenase (IDH)-mutant glioma cells. alpha-hydroxyglutarate 26-46 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-90 34985589-1 2022 OBJECTIVE: Oncometabolite D-2-hydroxyglutarate (2HG) is pooled in isocitrate dehydrogenase (IDH)-mutant glioma cells. alpha-hydroxyglutarate 26-46 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 92-95 35104795-3 2022 As patients with IDH-mutant glioma enter early-phase vaccine and immune checkpoint inhibitor clinical trials, there is emerging evidence that implicates the oncometabolite, 2-hydroxyglutarate (2HG), generated by the neomorphic activity of mutant IDH, as a potential barrier to current immunotherapeutic approaches. alpha-hydroxyglutarate 173-191 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 17-20 35104795-3 2022 As patients with IDH-mutant glioma enter early-phase vaccine and immune checkpoint inhibitor clinical trials, there is emerging evidence that implicates the oncometabolite, 2-hydroxyglutarate (2HG), generated by the neomorphic activity of mutant IDH, as a potential barrier to current immunotherapeutic approaches. alpha-hydroxyglutarate 173-191 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 246-249 35104795-3 2022 As patients with IDH-mutant glioma enter early-phase vaccine and immune checkpoint inhibitor clinical trials, there is emerging evidence that implicates the oncometabolite, 2-hydroxyglutarate (2HG), generated by the neomorphic activity of mutant IDH, as a potential barrier to current immunotherapeutic approaches. alpha-hydroxyglutarate 193-196 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 17-20 35104795-3 2022 As patients with IDH-mutant glioma enter early-phase vaccine and immune checkpoint inhibitor clinical trials, there is emerging evidence that implicates the oncometabolite, 2-hydroxyglutarate (2HG), generated by the neomorphic activity of mutant IDH, as a potential barrier to current immunotherapeutic approaches. alpha-hydroxyglutarate 193-196 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 246-249 35198955-4 2022 One possible etiology of the high rate of epileptogenicity in oligodendrogliomas is D-2-Hydroxyglutarate (D2HG), an oncometabolite seen in IDH mutation (8). alpha-hydroxyglutarate 84-104 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 139-142 35198955-4 2022 One possible etiology of the high rate of epileptogenicity in oligodendrogliomas is D-2-Hydroxyglutarate (D2HG), an oncometabolite seen in IDH mutation (8). alpha-hydroxyglutarate 106-110 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 139-142 34994387-2 2022 Here, we hypothesize that the active metabolite D-2-hydroxyglutarate (D-2-HG) produced by the IDH-mutant enzyme leads to metabolic disruptions in surrounding cortical neurons that consequently promote seizures. alpha-hydroxyglutarate 70-76 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 94-97