【摘 要】
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Pyruvate dehydrogenase kinase 1 (PDHK1) is a metabolic enzyme critically involved in switching glucose metabolism from mitochondrial oxidation to aerobic glycolysis in cancer cells.Increasing evidence
【机 构】
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肿瘤药理一室,药物研究国家重点实验室,上海药物所,中国科学院,上海,201203,中国 华东科技大
【出 处】
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2015医学前沿论坛暨第十四届全国肿瘤药理与化疗学术会议
论文部分内容阅读
Pyruvate dehydrogenase kinase 1 (PDHK1) is a metabolic enzyme critically involved in switching glucose metabolism from mitochondrial oxidation to aerobic glycolysis in cancer cells.Increasing evidences suggest that PDHK1 appears to be the Achilles heel in the reprogrammed glucose metabolism in cancer cells, thus targeting PDHK1 holds huge antitumor promise.In an effort to discover new PDHK1 inhibitors, we carried out an enzymatic screen using a small-molecule library.JX06 emerged prominently due to the remarkable activity against PDHK1.To examine whether JX06 specifically targeted PDHK1, JX06 activity was profiled in a board panel of 323 kinases, which covered most known kinases implicated in cancer malignancy.Among the tested kinases, only PDHKs were remarkably inhibited by JX06 at the concentration of 10 μM.At cellular level, JX06 decreased PDHK1 downstream in a time-and dose-dependent manner,resulting in a metabolic switch from aerobic glycolysis to oxidative phosphorylation.
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