Disodium (R)-2-Hydroxyglutarate

製品コードS7873 バッチS787305

印刷

化学情報

Chemical Structure Synonyms D-α-Hydroxyglutaric acid disodium Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C5H6Na2O5
分子量 192.08 CAS No. 103404-90-6
Solubility (25°C)* 体外 Water 38 mg/mL warmed with 50ºC water bath (197.83 mM)
DMSO Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Disodium (R)-2-Hydroxyglutarate (D-α-Hydroxyglutaric acid disodium) is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases with Ki of 0.628 mM.
in vitro 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. [1] Besides, (R)-2-Hydroxyglutarate inhibits ATP synthase and mTOR signaling, and thus causes growth arrest and tumor cell killing. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Enzymatic Assays
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 L- or 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 Fe(NH4)2(SO4)22, 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.
細胞アッセイ 細胞株 U87/IDH1(R132H), Octyl α-KG- or octyl 2-HG-treated U87, and HCT 116 IDH1(R132H/+) cells
濃度 ~800 μM
反応時間 4 days
実験の流れ

Cells are seeded in 12-well plates and, after overnight incubation, treated with the indicated concentrations of each compound. After harvesting, cells are stained with acridine orange (AO) and 4′,6-diamidino-2-phenylindole (DAPI). Cell number and viability are measured based on AO and DAPI fluorescence as measured by NC3000 following the manufacturer’s instructions.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming [ Nat Commun, 2023, 14(1):984] PubMed: 36849508
Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity [ Cell Mol Immunol, 2022, 10.1038/s41423-022-00842-9] PubMed: 35301470
D2HGDH-mediated D2HG catabolism enhances the anti-tumor activities of CAR-T cells in an immunosuppressive microenvironment [ Mol Ther, 2022, S1525-0016(22)00007-7] PubMed: 35007759
NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion [ Cell Metab, 2021, 33(1):110-127.e5] PubMed: 33171124
Wild-Type IDH1 and Mutant IDH1 Opposingly Regulate Podoplanin Expression in Glioma [ Transl Oncol, 2020, 13(4):100758] PubMed: 32208352
Isocitrate dehydrogenase1 mutation reduces the pericyte coverage of microvessels in astrocytic tumours [ J Neurooncol, 2019, 143(2):187-196] PubMed: 31004262
Cytokine correlation analysis based on drug perturbation [Wallner FK, et al. Cytokine, 2016, 90:73-79] PubMed: 27816795

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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