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

Animals Drug Discovery Enzyme Inhibitors / chemistry Lipase / antagonists & inhibitors Lipolysis / drug effects Mice Phenylurea Compounds / chemistry Structure-Activity Relationship Triglycerides / blood
Atglistatin Lipolysis NAFLD PNPLA2 Small molecule inhibitor

Journal

Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298

Informations de publication

Date de publication:
15 08 2020
Historique:
received: 29 03 2020
revised: 19 06 2020
accepted: 22 06 2020
entrez: 22 7 2020
pubmed: 22 7 2020
medline: 11 6 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.bmc.2020.115610 PMID: 32690265
pubmed: 32690265
pii: S0968-0896(20)30440-5
doi: 10.1016/j.bmc.2020.115610
pii:
doi:

Substances chimiques

Enzyme Inhibitors 0
Phenylurea Compounds 0
Triglycerides 0
atglistatin 0
Lipase EC 3.1.1.3
PNPLA2 protein, mouse EC 3.1.1.3

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

115610

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Nicole Mayer (N)

Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Martina Schweiger (M)

Institute of Molecular Biosciences, University of Graz, Heinrichstraße 31, A-8010 Graz, Austria; BIOTECHMED Graz, A-8010, Austria.

Elisabeth Fuchs (E)

Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Anna K Migglautsch (AK)

Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Carina Doler (C)

Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Gernot F Grabner (GF)

Institute of Molecular Biosciences, University of Graz, Heinrichstraße 31, A-8010 Graz, Austria.

Matthias Romauch (M)

Institute of Molecular Biosciences, University of Graz, Heinrichstraße 31, A-8010 Graz, Austria.

Michaela-Christina Melcher (MC)

Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.

Rudolf Zechner (R)

Institute of Molecular Biosciences, University of Graz, Heinrichstraße 31, A-8010 Graz, Austria; BIOTECHMED Graz, A-8010, Austria.

Robert Zimmermann (R)

Institute of Molecular Biosciences, University of Graz, Heinrichstraße 31, A-8010 Graz, Austria; BIOTECHMED Graz, A-8010, Austria. Electronic address: robert.zimmermann@uni-graz.at.

Rolf Breinbauer (R)

Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria; BIOTECHMED Graz, A-8010, Austria. Electronic address: breinbauer@tugraz.at.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Structure-activity relationship studies for...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Structure-activity relationship studies for...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Structure-activity relationship studies for...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Carboxylic ester hydrolases › Triacylglycerol lipase › Structure-activity relationship studies for...
questionsmedicales.fr › Métabolisme › Métabolisme lipidique › Lipolyse › Structure-activity relationship studies for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Structure-activity relationship studies for...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Phénylurées › Structure-activity relationship studies for...
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questionsmedicales.fr › Lipides › Glycérides › Triglycéride › Structure-activity relationship studies for...