Development of Small Molecule Inhibitors Targeting Human Adipose Triglyceride Lipase

Development of Small Molecule Inhibitors Targeting Human Adipose Triglyceride Lipase

Rolf Breinbauer (ORCID: 0000-0001-6009-7359)

Disciplines

Chemistry (75%); Medical-Theoretical Sciences, Pharmacy (25%)

Keywords

    Adipose Triglyceride Lipase, Medicinal Chemistry, Lipase Inhibitor, Insulin Resistance, Lipolysis, Organic Synthesis

Abstract

Adipose triglyceride lipase (ATGL) is required for efficient mobilization of fatty acids from cellular triglyceride stores. This central role in lipolysis marks ATGL as an interesting pharmacological target as deregulated fatty acid metabolism is closely linked to dyslipidemic and metabolic disorders. Based on preliminary structure-activity relationship (SAR) data we propose the design, synthesis, identification, and characterization of small-molecule inhibitors of human ATGL (hATGL). As no 3D- structure is yet available for ATGL, we will pursue a classic medicinal chemistry approach in which compounds will be synthesized and tested to establish the SAR and optimize the properties of the inhibitor. The resulting molecular probe will be of tremendous value for studying the role of hATGL in lipid metabolism and metabolic disorders.
Research institution(s)
Project participants

Research Output

  • 242 Citations
  • 11 Publications
  • 1 Fundings
Publications
  • 2022
    Title Small-Molecule Inhibitors Targeting Lipolysis in Human Adipocytes
    DOI 10.1021/jacs.1c10836
    Type Journal Article
    Author Grabner G
    Journal Journal of the American Chemical Society
    Pages 6237-6250
    Link Publication
  • 2019
    Title Zinc-a2-Glycoprotein Is An Inhibitor Of Amine Oxidase Copper-Containing 3
    DOI 10.1101/727214
    Type Preprint
    Author Romauch M
    Pages 727214
    Link Publication
  • 2019
    Title Plasma enhances AOC3 activity from Zinc-2-glycoprotein is an inhibitor of amine oxidase copper-containing 3.
    DOI 10.6084/m9.figshare.8868269.v2
    Type Other
    Author Romauch M
    Link Publication
  • 2019
    Title Plasma enhances AOC3 activity from Zinc-2-glycoprotein is an inhibitor of amine oxidase copper-containing 3
    DOI 10.6084/m9.figshare.8868269.v1
    Type Other
    Author Romauch M
    Link Publication
  • 2019
    Title Plasma enhances AOC3 activity from Zinc-2-glycoprotein is an inhibitor of amine oxidase copper-containing 3.
    DOI 10.6084/m9.figshare.8868269
    Type Other
    Author Romauch M
    Link Publication
  • 2019
    Title ROS induces ZAG oligomerization from Zinc-2-glycoprotein is an inhibitor of amine oxidase copper-containing 3.
    DOI 10.6084/m9.figshare.8868266
    Type Other
    Author Romauch M
    Link Publication
  • 2019
    Title ROS induces ZAG oligomerization from Zinc-2-glycoprotein is an inhibitor of amine oxidase copper-containing 3
    DOI 10.6084/m9.figshare.8868266.v1
    Type Other
    Author Romauch M
    Link Publication
  • 2019
    Title ROS induces ZAG oligomerization from Zinc-2-glycoprotein is an inhibitor of amine oxidase copper-containing 3.
    DOI 10.6084/m9.figshare.8868266.v2
    Type Other
    Author Romauch M
    Link Publication
  • 2017
    Title Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice
    DOI 10.1038/ncomms14859
    Type Journal Article
    Author Schweiger M
    Journal Nature Communications
    Pages 14859
    Link Publication
  • 2016
    Title Chemical Genetic Approaches for the Investigation of Neutral Lipid Metabolism
    DOI 10.1002/cbic.201500501
    Type Journal Article
    Author Doler C
    Journal ChemBioChem
    Pages 358-377
  • 2020
    Title Zinc-a2-glycoprotein as an inhibitor of amine oxidase copper-containing 3
    DOI 10.1098/rsob.190035
    Type Journal Article
    Author Romauch M
    Journal Open Biology
    Pages 190035
    Link Publication
Fundings
  • 2017
    Title Atglistatin für ATGL
    Type Research grant (including intramural programme)
    Start of Funding 2017