Disodium (R)-2-Hydroxyglutarate
(Synonyms: (R)-2-羟基戊二酸二钠盐; Disodium (R)-2-hydroxyglutarate) 目录号 : GC10981
An α-hydroxy acid
Cas No.:103404-90-6
Sample solution is provided at 25 µL, 10mM.
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Information here is from (R)-2-hydroxyglutarate ((R)-2HG) instead of Disodium (R)-2-Hydroxyglutarate. (R)-2HG inhibits adenosine triphosphate (ATP) synthase [1]. The IC50 value has not been found.
ATP synthase containing a rotary motor involved in energy conversion in organisms. It produces ATP from inorganic phosphate and adenosine diphosphate (ADP). It functions using the energy from a respiration- or photosynthesis-generated transmembrane proton-motive force [2].
Data showed that (R)-2HG accumulated in human cancers carrying mutant isocitrate dehydrogenase (IDH) 1 and 2 genes. In IDH1 mutant cells, the inhibition of (R)-2HG to ATP synthase was mirrored. This indicated that (R)-2HG has a growth-suppressive function. In glioblastoma cells, consistently, the inhibition of (R)-2HG to ATP synthase is sufficient for tumor cell killing and growth arrest under glucose limitation conditions, e.g., when ketone bodies are supplied for energy instead of glucose. In cells, treatment with (R)-2HG decreased the rate of ATP synthase-linked oxygen consumption [1].
The normal cellular concentration of (R)-2HG is 200 mM. At this concentration, ATP synthase is unlikely to be significantly inhibited by (R)-2HG. In glioma patients with IDH mutations, (R)-2HG accumulates to 10-100 times of normal levels, and ATP synthase would be possible to be inhibited. (R)-2HG extended the lifespan of C. elegans, in a similar way of α-KG. Data showed that 2-HG increased lifespan ATP-synthase-dependently [1].
References:
[1]. Fu X, Chin RM, Vergnes L, et al. 2-Hydroxyglutarate inhibits ATP synthase and mTOR signaling. Cell metabolism, 2015, 22(3): 508-515.
[2]. Stock D, Leslie AGW and Walker JE. Molecular architecture of the rotary motor in ATP synthase. Science, 1999, 286(5445): 1700-1705.
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Kinase experiment: |
To assay human JHDM1A/KDM2A demethylase activity toward H3K36me2, His tagged JHDM1A is first obtained by transforming pET28a-JHDM1A into Escherichia coli BL21 and protein expression is induced by addition of 1 mM IPTG at 30°C when cell density reaches 0.5 OD600 units. Cells are lysed by sonication and Ni-NTA agarose is used to purify His-JHDM1A fusion proteins. Histone demethylase assay is carried out by incubating 2 μg oligonucleosomes, 4 μg purified His-JHDM1A, and/or 10-50 mM D-2-HG in histone demethylation buffer [50 mM HEPES (pH 8.0), 625 μM Fe(NH4)2(SO4)2, 0.1-0.5 mM α-KG, 2 mM ascorbate] at 37°C for 2-3 hr and the reactions are stopped by the addition of SDS loading buffer and subsequently analyzed by western blotting using anti-H3K36me2 antibody. To measure CeKDM7A demethylase activity toward H3K9me2 and H3K27me2, two synthetic dimethylated peptides H3K9me2 [ARTKQTARK (me2)STGGKA] and H3K27me2 [QLATKAARK (me2)SAPAS] are used as substrates. Demethylase assays are carried out in the presence of 10 μg enzyme, 1 μg peptide in 20 μl buffer 20 mM Tris-HCl (pH 7.5), 150 mM NaCl, 50 μM (NH4)2Fe(SO4)2, 100 μM α-KG, 2 mM Vc, 10 mM PMSF for 3 hr. The demethylation reaction mixture is desalted by passing through a C18 ZipTip. To examine the inhibitory effect of 2-HG, various concentrations of 2-HG are incubated with KDM7A briefly before adding other reaction mixtures. The samples are analyzed by a MALDI-TOF/TOF mass spectrometer[1]. |
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Cell experiment: |
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-2-HG). 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]. |
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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. |
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| Cas No. | 103404-90-6 | SDF | |
| 别名 | (R)-2-羟基戊二酸二钠盐; Disodium (R)-2-hydroxyglutarate | ||
| 化学名 | sodium (R)-2-hydroxypentanedioate | ||
| Canonical SMILES | O[C@](C([O-])=O)([H])CCC([O-])=O.[Na+].[Na+] | ||
| 分子式 | C5H6Na2O5 | 分子量 | 192.08 |
| 溶解度 | 75mg/mL in Water (Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet