Fluorescent retinoid X receptor ligands for fluorescence polarization assay

Shoya Yamada, Fuminori Ohsawa, Shuji Fujii, Ryosuke Shinozaki, Makoto Makishima, Hirotaka Naitou, Shuichi Enomoto, Akihiro Tai, Hiroki Kakuta

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)5143-5146
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number17
Publication statusPublished - Sept 1 2010


  • Carbostyril
  • Fluorescence polarization
  • Molecular design
  • Retinoid X receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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