Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL)

Nicole Mayer, Martina Schweiger, Elisabeth Fuchs, Anna K. Migglautsch, Carina Doler, Gernot F. Grabner, Matthias Romauch,, Michaela Christina Melcher, Rudolf Zechner, Robert Zimmermann, Rolf Breinbauer*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD. In this article, we report about structure–activity relationship (SAR) studies of small molecule inhibitors of murine ATGL which led to the development of Atglistatin. Atglistatin is a specific inhibitor of murine ATGL, which has proven useful for the validation of ATGL as a potential drug target.

Original languageEnglish
Article number115610
JournalBioorganic and Medicinal Chemistry
Volume28
Issue number16
DOIs
Publication statusPublished - 15 Aug 2020

Keywords

  • Atglistatin
  • Lipolysis
  • NAFLD
  • PNPLA2
  • Small molecule inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fields of Expertise

  • Human- & Biotechnology

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