Octyl-α-ketoglutarate

无

A cell-permeable form of α-ketoglutarate

Hypoxia-inducible factor 1α (HIF-1α) turnover is initiated by prolyl hydroxylases (PHD), which hydroxylate proline residues on HIF-1α, facilitating ubiquitination. PHD activity is linked to the tricarboxylic acid (TCA) cycle, since the intermediate α-ketoglutarate is a PHD substrate and succinate and fumarate inhibit PHD. Mutations in enzymes associated with the TCA cycle occur in certain cancers.1 Octyl-α-ketoglutarate is a stable, cell-permeable form of α-ketoglutarate which accumulates rapidly and preferentially in cells with a dysfunctional TCA cycle.2 When used at 1 mM, it stimulates PHD activity, increasing HIF-1α turnover.2,3 In addition, octyl-α-ketoglutarate competitively blocks succinate- or fumarate-mediated inhibition of PHD.2

258.3

≥95%

2-氧代-1-戊二酸辛基酯≥95%杂质≤5%

α-KG octyl ester

OC(CCC(C(OCCCCCCCC)=O)=O)=O

C13H22O5

876150-14-0

≥ 1 year

DMF: 10 mg/ml DMSO: 10 mg/ml Ethanol: 20 mg/ml PBS (pH 7.2): 2 mg/ml

1.Gottlieb, E., and Tomlinson, I.P.M. Mitochondrial tumour suppressors: A genetic and biochemical update. Nature Reviews.Cancer 5, 857-866 (2005).
2.MacKenzie, E.D.,Selak, M.A.,Tennant, D.A., et al. Cell-permeating α-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Molecular and Cellular Biology 27(9), 3282-3289 (2007).
3.Zhao, S.,Lin, Y.,Xu, W., et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1α. Science 324(5924), 261-265 (2009).

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