Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening

Shoya Yamada, Mayu Kawasaki, Michiko Fujihara, Masaki Watanabe, Yuta Takamura, Maho Takioku, Hiromi Nishioka, Yasuo Takeuchi, Makoto Makishima, Tomoharu Motoyama, Sohei Ito, Hiroaki Tokiwa, Shogo Nakano, Hiroki Kakuta

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8809-8818
Number of pages10
JournalJournal of medicinal chemistry
Volume62
Issue number19
DOIs
Publication statusPublished - Oct 10 2019
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Yamada, S., Kawasaki, M., Fujihara, M., Watanabe, M., Takamura, Y., Takioku, M., Nishioka, H., Takeuchi, Y., Makishima, M., Motoyama, T., Ito, S., Tokiwa, H., Nakano, S., & Kakuta, H. (2019). Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening. Journal of medicinal chemistry, 62(19), 8809-8818. https://doi.org/10.1021/acs.jmedchem.9b00995