D-α-Hydroxyglutaric acid disodium(Synonyms: (R)-2-羟基戊二酸二钠盐; Disodium (R)-2-hydroxyglutarate)

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D-α-Hydroxyglutaric acid disodium (Synonyms: (R)-2-羟基戊二酸二钠盐; Disodium (R)-2-hydroxyglutarate) 纯度: ≥98.0%

D-α-Hydroxyglutaric acid disodium (Disodium (R)-2-hydroxyglutarate) 是神经代谢疾病 D-2-羟基戊二酸尿症中积累的主要代谢产物。D-α-Hydroxyglutaric acid disodium 是 α-酮戊二酸 (α-KG) 的弱竞争拮抗剂，可抑制多种 α-KG 依赖性双加氧酶 (dioxygenases)，Ki 为 10.87 mM。D-α-Hydroxyglutaric acid disodium 可增加活性氧 (ROS) 的产生。D-α-Hydroxyglutaric acid disodium 还可结合并抑制 ATP 合酶并抑制 mTOR 信号传导。

D-α-Hydroxyglutaric acid disodium(Synonyms: (R)-2-羟基戊二酸二钠盐; Disodium (R)-2-hydroxyglutarate)

D-α-Hydroxyglutaric acid disodium Chemical Structure

CAS No. : 103404-90-6

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生物活性

D-α-Hydroxyglutaric acid disodium (Disodium (R)-2-hydroxyglutarate) is the principal metabolite accumulating in neurometabolic disease D-2-hydroxyglutaric aciduria. D-α-Hydroxyglutaric acid disodium is a weak competitive antagonist of α-ketoglutarate (α-KG) and inhibits multiple α-KG-dependent dioxygenases with a Ki of 10.87 mM. D-α-Hydroxyglutaric acid disodium increases reactive oxygen species (ROS) production. D-α-Hydroxyglutaric acid disodium binds and inhibits ATP synthase and inhibits mTOR signaling[1][2][3][4][5].

IC50 & Target

Ki: 10.87 mM (α-KG-dependent dioxygenases)[1]
ATP synthase[2]
mTOR[2]
Reactive oxygen species (ROS) [5]
体外研究
(In Vitro)

D-α-Hydroxyglutaric acid ((R)-2-hydroxyglutarate) accumulates in human cancers carrying neomorphic mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes[1][2].
A partial inhibition of KDM7A toward both H3K9me2 and H3K27me2 peptides is observed in the presence of 50 mM D-2-HG and 100 μM α-ketoglutarate (α-KG). Addition of 300 μM α-KG is capable of reversing the inhibition of Caenorhabditis elegans KDM7A (CeKDM7A) by 50 mM D-2-HG, indicating that D-2-HG is a weak competitive inhibitor against α-KG toward the CeKDM7A demethylase[1].
D-α-Hydroxyglutaric acid is a weak inhibitor of TET hydroxylases. In the presence of 0.1 mM of α-KG, addition of 10 mM D-α-Hydroxyglutaric acid results in a partial (33%) inhibition of TET2 and addition of 50 mM D-α-Hydroxyglutaric acid results in more inhibition (83%) of TET2. D-α-Hydroxyglutaric acid exhibits a less pronounced inhibitory effect toward TET1[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究
(In Vivo)

D-α-Hydroxyglutaric acid strongly inhibits glucose utilization, CO2 production and the respiratory chain in rat cerebral cortex and human skeletal muscle, as well as in submitochondrial particles from bovine heart, suggesting an impairment of the aerobic metabolism[5].
D-α-Hydroxyglutaric acid has also been proposed as an endogenous excitotoxic organic acid because it significantly decreased cell viability in neuronal cultures from chick embryo telencephalons and from neonatal rat hippocampus through stimulation of specific NMDA glutamate receptors[5].
D-α-Hydroxyglutaric acid (0.01-1 mM) significantly increases chemiluminescence and thiobarbituric acid-reactive substances (TBA-RS) and decreased total antioxidant reactivity (TAR) values in the cortical supernatants in 30-day-old-rats[5].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量

192.08

Formula

C5H6Na2O5
CAS 号

103404-90-6
中文名称

D-α-羟基戊二酸二钠盐；(R)-2-羟基戊二酸二钠盐
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
溶解性数据
In Vitro: 

H2O : 75 mg/mL (390.46 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 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

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
参考文献

  • [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):2017-22.
Cell Assay
[2]

U87 cells, HCT 116 IDH1(R132H/+) cells, and HEK 293 cells are seeded in 12-well plates and after overnight incubation are treated with indicated concentrations of each compound (e.g., 400 and 800 μM D-α-Hydroxyglutaric acid). After harvesting, cells are stained with Acridine Orange (AO) and DAPI. Cell number and viability are measured based on AO and DAPI fluorescence measured by NC3000[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献

  • [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):2017-22.

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