Abstract
Pyruvate dehydrogenase kinases (PDKs) have recently emerged as an attractive target for cancer therapy. Herein, we prepared a series of compounds derived from dichloroacetate (DCA) which inhibited cancer cells proliferation. For the first time, we have successfully developed DCA derived inhibitors that preferentially bind to the adenosine triphosphate (ATP) pocket of PDK isoform 1 (PDK1).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism*
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Apoptosis / drug effects*
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / enzymology
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Breast Neoplasms / pathology
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Cell Proliferation / drug effects*
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Dichloroacetic Acid / chemistry*
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Drug Discovery*
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Female
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Flow Cytometry
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Humans
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Membrane Potential, Mitochondrial / drug effects
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Phosphorylation / drug effects
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
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Tumor Cells, Cultured
Substances
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PDK1 protein, human
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
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Adenosine Triphosphate
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Dichloroacetic Acid
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Protein Serine-Threonine Kinases