Structure-guided development of specific pyruvate dehydrogenase kinase inhibitors targeting the ATP-binding pocket

Shih Chia Tso, Xiangbing Qi, Wen Jun Gui, Cheng Yang Wu, Jacinta L. Chuang, Ingrid Wernstedt-Asterholm, Lorraine K. Morlock, Kyle R. Owens, Philipp E. Scherer, Noelle S. Williams, Uttam K. Tambar, R. Max Wynn, David T. Chuang

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Background: Up-regulated pyruvate dehydrogenase kinase isoforms (PDKs) are associated with impaired glucose homeostasis in diabetes. Results: Novel PDK inhibitors were developed using structure-based design, which improves glucose tolerance with reduced hepatic steatosis in diet-induced obese mice. Conclusion: Obesity phenotypes are effectively treated by chemical intervention with PDK inhibitors. Significance: PDKs are potential drug targets for obesity and type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)4432-4443
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number7
DOIs
StatePublished - Feb 14 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Structure-guided development of specific pyruvate dehydrogenase kinase inhibitors targeting the ATP-binding pocket'. Together they form a unique fingerprint.

  • Cite this