title: Unexpected Discovery of Dichloroacetate Derived Adenosine Triphosphate Competitors Targeting Pyruvate Dehydrogenase Kinase To Inhibit Cancer Proliferation.
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).
authors.affiliation: Drug Development Core, Faculty of Health Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Shao-Lin
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: Drug Development Core, Faculty of Health Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Hu
authors.affiliation: Drug Development Core, Faculty of Health Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Drug Development Core, Faculty of Health Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Kin Yip
authors.initials: KY
authors.lastname: Tam
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D003999:Dichloroacetic Acid / Q000737:chemistry*; D055808:Drug Discovery; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014407:Tumor Cells, Cultured
chemical_list: C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D000255:Adenosine Triphosphate; D003999:Dichloroacetic Acid; D017346:Protein Serine-Threonine Kinases