Compilation and evaluation of a fatty acid mimetics screening library

Ehrler, Johanna H. M.; Brunst, Steffen; Tjaden, Amelie; Kilu, Whitney; Heering, Jan; Hernandez-Olmos, Victor; Krommes, Andre; Kramer, Jan S.; Steinhilber, Dieter; Schubert-Zsilavecz, Manfred; Müller, Susanne; Merk, Daniel und Proschak, Ewgenij (2022): Compilation and evaluation of a fatty acid mimetics screening library. In: Biochemical Pharmacology, Bd. 204, 115191

Abstract

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 gamma (PPAR gamma) and retinoid X receptor alpha (RXR alpha), 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0006-2952
• Sprache: Englisch