| CAS NO: | 876150-14-0 |
| 包装 | 价格(元) |
| 5mg (solution) | 电议 |
| 10mg (solution) | 电议 |
| Physical Appearance | A solution in acetate. To change the solvent, simply evaporate the acetate containing under a gentle stream of nitrogen and immediately add the solvent of choice. |
| Storage | Store at -20°C |
| M.Wt | 258.3 |
| Cas No. | 876150-14-0 |
| Formula | C13H22O5 |
| Synonyms | α-KG octyl ester |
| Solubility | ≤20mg/ml in ethanol;10mg/ml in DMSO;10mg/ml in dimethyl formamide |
| Chemical Name | 2-oxo-pentanedioic acid, 1-octyl ester |
| Canonical SMILES | OC(CCC(C(OCCCCCCCC)=O)=O)=O |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。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。 |
Octyl-α-ketoglutarate is a stable, cell-permeable form of α-ketoglutarate, a substrate of prolyl hydroxylases (PHD) [1][2].
The high turnover of HIFα is initiated by prolyl hydroxylases (PHD), which hydroxylate proline residues on the oxygen-dependent degradation (ODD) domain of HIFα, facilitating ubiquitination and degradation. To catalyze proline hydroxylation, PHDs convert molecular oxygen and α-ketoglutarate to carbon dioxide and succinate [2]. Loss of IDH1 activity would reduce cellular levels of α-KG [3].
Octyl-α-ketoglutarate is a cell-permeating α-ketoglutarate derivative, which built up rapidly and preferentially in cells with a dysfunctional TCA cycle. Octyl-α-ketoglutarate increased intracellular levels of freeα-ketoglutaric acid by approximately fourfold. In HEK293-derived cell lines expressing both a GFP-ODD fusion protein and HA-tagged pVHL, Octyl-α-ketoglutarate reactivated PHD activity inhibited by succinate or fumarate. Octyl-α-ketoglutarate restored hydroxylation and targeted HIF1 for ubiquitylation and proteasomally mediated degradation [2]. Octyl-α-ketoglutarate inhibited the HIF-1α induction caused by IDH1 knockdown in HeLa cells or overexpression of IDH1R132H mutant in U-87MG cells, suggesting a reduction in IDH1 activity caused a reduction in α-KG levels that in turn led to stabilization of HIF-1α [3].
References:
[1]. Gottlieb E, Tomlinson IP. Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer. 2005 Nov;5(11):857-66.
[2]. MacKenzie ED, Selak MA, Tennant DA, et al. Cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Mol Cell Biol. 2007 May;27(9):3282-9.
[3]. Zhao S, Lin Y, Xu W, et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science. 2009 Apr 10;324(5924):261-5.
m.cnreagent.com