2. Academic Validation
  3. Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening

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

  • J Med Chem. 2019 Oct 10;62(19):8809-8818. doi: 10.1021/acs.jmedchem.9b00995.
Shoya Yamada 1 2,  Mayu Kawasaki 3,  Michiko Fujihara 1 4,  Masaki Watanabe 1,  Yuta Takamura 1,  Maho Takioku 1,  Hiromi Nishioka 1,  Yasuo Takeuchi 1,  Makoto Makishima 5,  Tomoharu Motoyama 3,  Sohei Ito 3,  Hiroaki Tokiwa,  Shogo Nakano 3,  Hiroki Kakuta 1
Affiliations

Affiliations

  • 1 Division of Pharmaceutical Sciences , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , 1-1-1, Tsushima-naka , Kita-ku, Okayama 700-8530 , Japan.
  • 2 Research Fellowship Division , Japan Society for the Promotion of Science , Sumitomo-Ichibancho FS Bldg., 8 Ichibancho , Chiyoda-ku, Tokyo 102-8472 , Japan.
  • 3 Graduate School of Integrated Pharmaceutical and Nutritional Sciences , University of Shizuoka , 52-1 Yada , Suruga-ku, Shizuoka 422-8526 , Japan.
  • 4 AIBIOS Co. Ltd. , Tri-Seven Roppongi 8F 7-7-7 Roppongi , Minato-ku, Tokyo 106-0032 Japan.
  • 5 Division of Biochemistry, Department of Biomedical Sciences , Nihon University School of Medicine , 30-1 Oyaguchi-kamicho , Itabashi-ku, Tokyo 173-8610 , Japan.
PMID: 31483660 DOI: 10.1021/acs.jmedchem.9b00995
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-180351
    Fluorescent RXR Agonist