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Octyl-α-ketoglutarate

In stock
Catalog No.
C4321
prolyl hydroxylases (PHD) activator
Grouped product items
SizePriceStock Qty
5mg
$205.00
In stock
10mg
$365.00
In stock

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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.

Chemical Properties

Physical AppearanceA solution in methyl acetate
StorageStore at -20°C
M.Wt258.3
Cas No.876150-14-0
FormulaC13H22O5
Synonymsα-KG octyl ester
Solubility≤20mg/ml in ethanol;10mg/ml in DMSO;10mg/ml in dimethyl formamide
Chemical Name2-oxo-pentanedioic acid, 1-octyl ester
SDFDownload SDF
Canonical SMILESOC(CCC(C(OCCCCCCCC)=O)=O)=O
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Quality Control

Quality Control & MSDS

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Chemical structure

Octyl-α-ketoglutarate