| 生物活性： |
靶点：α-ketoglutarate-dependent dioxygenases
通路：Metabolic Enzyme&Protease
背景说明：Disodium (R)-2-Hydroxyglutarate是一种稍弱的竞争性 α-酮戊二酸 (α-KG) 依赖性双加氧酶抑制剂。
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[1-5].
IC50：Ki: 10.87 mM (α-KG-dependent dioxygenases)[1]
In Vitro：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].
In Vivo：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].
细胞实验：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].
动物实验：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].
数据来源文献：[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 B?ttcher， 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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| 其它标识： |
MDL：MFCD00069573
SMILES：O=C([O-])[C@H](O)CCC([O-])=O.[Na+].[Na+]
InChIKey：DZHFTEDSQFPDPP-HWYNEVGZSA-L
InChI：InChI=1S/C5H8O5.2Na/c6-3(5(9)10)1-2-4(7)8;;/h3,6H,1-2H2,(H,7,8)(H,9,10);;/q;2*+1/p-2/t3-;;/m1../s1
PubChem CID：51051608
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| 基本信息： |
CAS：103404-90-6
中文名称：2-羟基-D-谷氨酸二钠盐
英文名称：Disodium (R)-2-Hydroxyglutarate
别名：(R)-2-羟基戊二酸二钠盐;(R)-2-羟基戊二酸
分子式：C5H6O5Na2
分子量：192.08
规格：10mg
溶解性：Soluble in Water ≥2mg/mL
纯度：≥98%
外观(性状)：White to yellow Solid
储存条件：Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
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| 靶点： |
α-ketoglutarate-dependent dioxygenases |
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