Octyl-α-ketoglutarate is a stable, cell-permeable form of α-ketoglutarate, a substrate of prolyl hydroxylases (PHD) .
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 . Loss of IDH1 activity would reduce cellular levels of α-KG .
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 . 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 .
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|Physical Appearance||A solution in methyl acetate|
|Storage||Store at -20°C|
|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|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For 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.|