title: Fluorescent retinoid X receptor ligands for fluorescence polarization assay.
abstract: Retinoid X receptor (RXR) agonists are candidate agents for the treatment of metabolic syndrome and type 2 diabetes via activation of peroxisome proliferator-activated receptor (PPAR)/RXR or liver X receptor (LXR)/RXR-heterodimers, which control lipid and glucose metabolism. Reporter gene assays or binding assays with radiolabeled compounds are available for RXR ligand screening, but are unsuitable for high-throughput screening. Therefore, as a first step towards stabilizing a fluorescence polarization (FP) assay system for high-throughput RXR ligand screening, we synthesized fluorescent RXR ligands by modification of the lipophilic domain of RXR ligands with a carbostyril fluorophore, and selected the fluorescent RXR agonist 6-[ethyl(1-isobutyl-2-oxo-4-trifluoromethyl-1,2-dihydroquinolin-7-yl)amino]nicotinic acid 8d for further characterization. Compound 8d showed FP in the presence of RXR and the FP was decreased in the presence of the RXR agonist LGD1069 (2). This compound should be a lead compound for use in high-throughput assay systems for screening RXR ligands.
authors.affiliation: Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-Naka, Okayama, Japan.
authors.forename: Shoya
authors.initials: S
authors.lastname: Yamada
authors.forename: Fuminori
authors.initials: F
authors.lastname: Ohsawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Fujii
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Shinozaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Makishima
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Naitou
authors.forename: Shuichi
authors.initials: S
authors.lastname: Enomoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kakuta
mesh_terms: D019281:Dimerization; D005454:Fluorescence Polarization; D008024:Ligands; D047488:Retinoid X Receptors / Q000378:metabolism*
chemical_list: D008024:Ligands; D047488:Retinoid X Receptors