AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2

Biochem Soc Trans. 2003 Dec;31(Pt 6):1168-70. doi: 10.1042/bst0311168.

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.

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology*
  • Liver / drug effects
  • Liver / enzymology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / enzymology
  • Protein Kinase Inhibitors*
  • Protein Kinases*
  • Protein Serine-Threonine Kinases
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Rats
  • Rats, Wistar

Substances

  • Enzyme Inhibitors
  • Protein Kinase Inhibitors
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Protein Kinases
  • Protein Serine-Threonine Kinases