RXR ligands are candidate agents for the treatment of type 2 diabetes, because they can control lipid- or glucose-metabolic controlling nuclear receptor functions (PPARs, LXRs etc.). However, since current methods for screening of RXR ligands need cost and complicated handling. First screening for RXR ligands remains inefficient. These backgrounds prompted us to create a simple and inexpensive RXR ligand screening system such as fluorescence polarization (FP) assay using fluorescent ligands. Though we have reported fluorescent RXR agonists, their fluorescent properties and RXR binding potencyies remain unsatisfied. In this research, we discovered 6-[N-ethyl-N-(5-isobutoxy-4-isopropyl-2-(E)-styrylphenyl)amino]nicotinic acid (NEt-SB) as a fluorescent RXR antagonist (Ex: 299 nm, Em: 435 nm). In addition, we performed FP assay using NEt-SB (100 nM) in the presence of RXR (0.1 mg/mL) and evaluated the RXR binding affinities of several RXR ligands. As a result, the correlation between FP assay employing NEt-SB and reporter gene assay was observed.

Discovery and application of a fluorescent RXR antagonist to fluorescence polarization assay

244th National Meeting (2012)

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