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

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

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

doi

10.1021/acs.jmedchem.9b00995

subject

Has Abstract

pub_date

2019-10-10 00:00:00

pages

8809-8818

issue

19

eissn

0022-2623

issn

1520-4804

journal_volume

62

pub_type

杂志文章

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