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Disodium (R)-2-Hydroxyglutarate

2-羟基-D-谷氨酸二钠盐
Catalog No.
B6018
α酮戊二酸依赖性的双加氧酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL H2O)
¥ 454.00
现货
25mg
¥ 636.00
现货
50mg
¥ 1,090.00
现货
100mg
¥ 1,909.00
现货

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A

背景

这里使用(R)-2-hydroxyglutarate ((R)-2HG)代替Disodium (R)-2-Hydroxyglutarate。(R)-2HG抑制腺苷三磷酸(ATP)合成酶[1]。IC50值没有测定结果。

ATP合酶含有旋转马达,参与生物能量转换。它促使无机磷酸盐和腺苷二磷酸(ADP)产生ATP。它主要是从呼吸作用或光合作用产生的跨膜质子原动力的能量来产生作用[2]。

数据表明,(R)-2HG在携带突变异柠檬酸脱氢酶(IDH)1和2的基因的人类癌症中累积。在IDH1突变的细胞中,(R)-2HG抑制ATP合酶。这表明(R)-2HG具有生长抑制功能。在胶质母细胞瘤细胞中,(R)-2HG对ATP合酶的抑制足以杀死肿瘤细胞,并在葡萄糖限制条件下停滞生长,例如,当酮体替代葡萄糖提供能量。在细胞中,(R)-2HG降低了ATP合酶相关的耗氧速率[1]。

(R)-2HG的正常细胞的浓度为200 mM。在该浓度下,(R)-2HG不太可能显著地抑制ATP合酶。在IDH突变的神经胶质瘤患者中,(R)-2HG累积到正常水平的10-100倍,可能抑制 ATP合酶。(R)-2HG用α-KG相似的方式延长了线虫的寿命。数据表明,2-HG增加依赖性ATP合成酶的寿命[1]。

参考文献:
[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.

化学属性

Physical AppearanceA solid
StorageStore at -20°C
M.Wt192.08
Cas No.103404-90-6
FormulaC5H6Na2O5
Solubilityinsoluble in EtOH; insoluble in DMSO; ≥9.1 mg/mL in H2O
Chemical Namesodium (R)-2-hydroxypentanedioate
SDFDownload SDF
Canonical SMILESO[C@](C([O-])=O)([H])CCC([O-])=O.[Na+].[Na+]
运输条件 蓝冰运输或根据您的需求运输。
一般建议不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。

试验操作

Cell experiment:[1]

Cell lines

TF-1 cells

Reaction Conditions

100 ~ 500 μM (R)-2HG for 0 ~ 12 d incubation

Applications

TF-1 cells passaged in the presence of the cell membrane-permeable version of (R)-2HG became growth factor-independent and no longer differentiated in response to erythropoietin (EPO). Promotion of growth factor-independence and loss of EPO-responsiveness by (R)-2HG was dose-dependent and passage-dependent. (R)-2HG was sufficient to promote leukemogenesis and its effects were reversible.

Note

The technical data provided above is for reference only.

References:

1. Losman JA, Looper RE, Koivunen P, et al. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science, 2013, 339(6127): 1621-1625.

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