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| 10mg |
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| 25mg |
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Purity: ≥98%
Disodium (R)-2-Hydroxyglutarate (also known as D-2-HGA, or 2-HG) is a potent and competitive inhibitor of α-ketoglutarate (α-KG)-dependent dioxygenases with Ki value of 0.628 mM. In U-87MG cells, (R)-2-Hydroxyglutarate acts as weak antagonists of α-KG to inhibit α-KG-dependent histone demethylases and increases dimethylation on both H3K9 and H3K79. Besides, (R)-2-Hydroxyglutarate also inhibits ATP synthase and mTOR signaling, and therefore causes growth arrest and tumor cell killing. Inhibition of ATP synthase by 2-HG or α-KG in glioblastoma cells is sufficient for growth arrest and tumor cell killing under conditions of glucose limitation, e.g., when ketone bodies (instead of glucose) are supplied for energy. These findings inform therapeutic strategies and open avenues for investigating the roles of 2-HG and metabolites in biology and disease.
| ln Vitro |
Isocitrate dehydrogenase (IDH) 1 and 2 gene mutations cause the accumulation of D-α-hydroxyglutaric acid disodium ((R)-2-hydroxyglutarate) in human malignancies [1][2]. KDM7A partially inhibited H3K9me2 and H3K27me2 peptides when 50 mM D-2-HG and 100 μM α-ketoglutarate (α-KG) were present. If 300 μM α-KG is added, it can counteract the inhibitory action of 50 mM D-2-HG on CeKDM7A, proving that D-α-Hydroxyglutaric acid disodium is merely a weak competitive inhibitor of α-KG directed at CeKDM7A demethylase[1]. TET hydroxylase is weakly inhibited by D-α-Hydroxyglutaric acid disodium. When 10 mM D-α-hydroxyglutarate was added in the presence of 0.1 mM α-KG, TET2 was partially (33%) inhibited, and higher inhibition (83%) was observed when 50 mM D-α-hydroxyglutarate was added. TET1 is less obviously inhibited by D-α-hydroxyglutaric acid [1].
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| ln Vivo |
In rat cerebral cortex, human skeletal muscle, and bovine heart mitochondrial granules, D-α-hydroxyglutaric acid significantly inhibits glucose utilization, CO2 generation, and the respiratory chain, indicating decreased aerobic metabolism [5]. Due to its ability to stimulate the particular NMDA glutamate receptor, D-α-hydroxyglutaric acid is also regarded as an endogenous excitotoxic organic acid since it severely lowers cell survival in cultures of chick embryo telencephalon and newborn rat hippocampus neurons[5]. In the cortical supernatants of 30-day-old rats (TAR) value, D-α-Hydroxyglutaric acid disodium (0.01-1 mM) significantly reduces overall antioxidant reactivity and enhances chemiluminescence and thiobarbituric acid-reactive substances (TBA-RS)[5].
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| References |
[1]. Xu W, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011 Jan 18;19(1):17-30.
[2]. Fu X, et al. 2-Hydroxyglutarate Inhibits ATP Synthase and mTOR Signaling. Cell Metab. 2015 Sep 1;22(3):508-15. [3]. Martijn Kranendijk, et al. Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis. 2012 Jul;35(4):571-87. [4]. Martin Böttcher, et al. D-2-hydroxyglutarate interferes with HIF-1α stability skewing T-cell metabolism towards oxidative phosphorylation and impairing Th17 polarization. Oncoimmunology. 2018 Mar 26;7(7):e1445454. [5]. Alexandra Latini , et al. D-2-hydroxyglutaric acid induces oxidative stress in cerebral cortex of young rats. Eur J Neurosci. 2003 May;17(10):2017-2 |
| Molecular Formula |
C5H6NA2O5
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| Molecular Weight |
192.08
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| CAS # |
103404-90-6
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| Related CAS # |
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| SMILES |
O=C([O-])[C@H](O)CCC([O-])=O.[Na+].[Na+]
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| Chemical Name |
2R-hydroxy-pentanedioic acid, disodium salt
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| Synonyms |
D-alpha-Hydroxyglutaric acid disodium salt; Disodium (R)-2-hydroxyglutarate; D-2-HGA; 2R-hydroxy-pentanedioic acid, disodium salt
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (520.62 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.2062 mL | 26.0308 mL | 52.0616 mL | |
| 5 mM | 1.0412 mL | 5.2062 mL | 10.4123 mL | |
| 10 mM | 0.5206 mL | 2.6031 mL | 5.2062 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 2-HG extends the lifespan of adultC. elegans.Cell Metab.2015 Sep 1;22(3):508-15. |
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2-HG binds and inhibits ATP synthase.Cell Metab.2015 Sep 1;22(3):508-15. |
Inherent vulnerability, or the loss of cell viability, characteristic of cells with ATP5B knockdown, 2-HG accumulation, or IDH mutations.Cell Metab.2015 Sep 1;22(3):508-15. |
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