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Dimethyl 2-ketoglutarate is an esterified form of the citric acid cycle intermediate α-ketoglutarate.1 It increases intracellular levels of α-ketoglutarate and decreases intracellular ATP levels in U2OS human osteosarcoma cells cultured in complete- or nutrient-free media when used at a concentration of 5 mM.2 Dimethyl 2-ketoglutarate inhibits autophagy and decreases in intracellular levels of acetyl-CoA in serum- and nutrient-deprived cells.3 It decreases cardiomyocyte hypertrophy in a mouse model of cardiac pressure overload induced by thoracic aortic constriction when administered at a dose of 300 mg/kg. Dimethyl 2-ketoglutarate reduces serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and hepatic fibrosis in a rat model of liver fibrosis induced by carbon tetrachloride (CCl4).1

1.Zhao, J., Peng, L., Cui, R., et al.Dimethyl α-ketoglutarate reduces CCl4-induced liver fibrosis through inhibition of autophagy in hepatic stellate cellsBiochem. Biophys. Res. Commun.481(1-2)90-96(2021) 2.Baracco, E.E., Castoldi, F., Durand, S., et al.α-Ketoglutarate inhibits autophagyAging (Albany NY)11(11)3418-3431(2021) 3.MariÑo, G., Pietrocola, F., Eisenberg, T., et al.Regulation of autophagy by cytosolic acetyl-coenzyme AMol. Cell53(5)710-725(2014)

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