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: J A Morrell, J Orme, R J Butlin, T E Roche, R M Mayers, E Kilgour
• Journal: Biochemical Society transactions (Biochem Soc Trans) Vol. 31 Issue Pt 6 Pg. 1168-70 (Dec 2003) ISSN: 0300-5127 [Print] England
• PMID: 14641019 (Publication Type: Journal Article)

Chemical References

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

Topics

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