American Chemical Society Acta Medica Okayama 00222623 62 19 2019 Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening 8809 8818 EN Shoya Yamada Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Kawasaki Michiko Fujihara Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Watanabe Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Takamura Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Maho Takioku Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromi Nishioka Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Takeuchi Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makoto Makishima Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine Tomoharu Motoyama Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Sohei Ito Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Hiroaki Tokiwa Department of Chemistry and Research Center of Smart Molecules, Rikkyo University Shogo Nakano Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka Hiroki Kakuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2H-chromene-3-carboxylic acid (10, CU-6PMN) as a new fluorescent RXR agonist and developed a screening system of rexinoids using 10. Compound 10 was designed based on the fact that umbelliferone emits strong fluorescence in a hydrophilic environment, but the fluorescence intensity decreases in hydrophobic environments such as the interior of proteins. The developed assay using 10 enabled screening of rexinoids to be performed easily within a few hours by monitoring changes of fluorescence intensity with widely available fluorescence microplate readers, without the need for processes such as filtration. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2004 Salicylaldehyde類とWittig 試薬を用いた coumarin 環合成における置換基の影響に関する研究 EN Hiromi Nishioka No potential conflict of interest relevant to this article was reported.