title: AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2.
abstract: The PDH (pyruvate dehydrogenase) multi-enzyme complex catalyses a key regulatory step in oxidative glycolysis. Phosphorylation of the E1 subunit of the complex on serine residues results in the inactivation of enzyme activity. A family of four dedicated PDH kinase isoenzymes exists, each of which displays a distinct tissue-specific expression profile. AZD7545 is one of a series of PDH kinase inhibitors developed for the treatment of type 2 diabetes. The isoenzyme-selectivity profile of AZD7545 and related compounds is described and the consequences for their in vivo mode of action are discussed.
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, U.K.
authors.forename: J A
authors.initials: JA
authors.lastname: Morrell
authors.forename: J
authors.initials: J
authors.lastname: Orme
authors.forename: R J
authors.initials: RJ
authors.lastname: Butlin
authors.forename: T E
authors.initials: TE
authors.lastname: Roche
authors.forename: R M
authors.initials: RM
authors.lastname: Mayers
authors.forename: E
authors.initials: E
authors.lastname: Kilgour
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases