Compilation and evaluation of a fatty acid mimetics screening library.

Epoxide Hydrolases / metabolism Fatty Acid-Binding Proteins Fatty Acids / metabolism PPAR gamma / metabolism Receptors, Leukotriene B4 / metabolism Retinoid X Receptor alpha / metabolism
Fatty acid mimetics Focused screening libraries Lipid mediators Privileged scaffolds

Journal

Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032

Informations de publication

Date de publication:
10 2022
Historique:
received: 30 05 2022
revised: 21 07 2022
accepted: 22 07 2022
pubmed: 31 7 2022
medline: 12 10 2022
entrez: 30 7 2022
Statut: ppublish

Résumé

Focused compound libraries are well-established tools for hit identification in drug discovery and chemical probe development. We present the compilation and application of a focused screening library of fatty acid mimetics (FAMs), which are compounds designed to bind the orthosteric site of proteins that endogenously accommodate natural fatty acids and lipid metabolites. This set complies with chemical properties of FAM and was found suitable for use also in cellular setting. Several hits were retrieved in screening the focused library against diverse fatty acid binding targets including the enzymes soluble epoxide hydrolase (sEH) and leukotriene A4 hydrolase (LTA4H), the nuclear receptors peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RXRα), the carrier proteins fatty acid binding protein 4 and 5 (FABP4 and FABP5), as well as the G-protein coupled receptors leukotriene B4 receptor 1 (BLT1) and free-fatty acid receptor 1 (FFAR1). Thus, the focused FAM library is suitable to obtain chemical starting matter for fatty acid binding proteins and provides a valuable extension to available screening collections.

Identifiants

DOI: 10.1016/j.bcp.2022.115191 PMID: 35907497
pubmed: 35907497
pii: S0006-2952(22)00285-4
doi: 10.1016/j.bcp.2022.115191
pii:
doi:

Substances chimiques

Fatty Acid-Binding Proteins 0
Fatty Acids 0
PPAR gamma 0
Receptors, Leukotriene B4 0
Retinoid X Receptor alpha 0
Epoxide Hydrolases EC 3.3.2.-

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

115191

Informations de copyright

Copyright © 2022. Published by Elsevier Inc.

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

Johanna H M Ehrler (JHM)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.

Steffen Brunst (S)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany.

Amelie Tjaden (A)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences and Structural Genomics Consortium (SGC), Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany.

Whitney Kilu (W)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany.

Jan Heering (J)

Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany.

Victor Hernandez-Olmos (V)

Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany.

Andre Krommes (A)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.

Jan S Kramer (JS)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.

Dieter Steinhilber (D)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany.

Manfred Schubert-Zsilavecz (M)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.

Susanne Müller (S)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences and Structural Genomics Consortium (SGC), Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany.

Daniel Merk (D)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany; Ludwig-Maximilians-Universität München, Department of Pharmacy, Butenandtstr. 5-13, 81377 Munich, Germany.

Ewgenij Proschak (E)

Institute of Pharmaceutical Chemistry, Goethe-University, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany. Electronic address: proschak@pharmchem.uni-frankfurt.de.

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Epoxide hydrolase › Compilation and evaluation of a fatty acid...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Protéines de liaison aux acides gras › Compilation and evaluation of a fatty acid...
questionsmedicales.fr › Lipides › Acides gras › Compilation and evaluation of a fatty acid...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteur PPAR gamma › Compilation and evaluation of a fatty acid...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › Récepteurs aux éicosanoïdes › Récepteurs aux leucotriènes › Récepteurs aux leucotriènes B4 › Compilation and evaluation of a fatty acid...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteur des rétinoïdes X type alpha › Compilation and evaluation of a fatty acid...