ID | 66178 |
著者 |
Miura, Kizuku
Faculty of Pharmaceutical Sciences, Okayama University
Fujihara, Michiko
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Watanabe, Masaki
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takamura, Yuta
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kawasaki, Mayu
Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka
Nakano, Shogo
Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka
Kakuta, Hiroki
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | High selectivity of small-molecule drug candidates for their target molecule is important to minimize potential side effects. One factor that contributes to the selectivity is the internal polarity of the ligand-binding pocket (LBP) in the target molecule, but this is difficult to measure. Here, we first confirmed that the retinoid X receptor (RXR) agonist 6-(ethyl(1-isobutyl-2-oxo-4-(trifluoromethyl)-1,2-dihydroquinolin-7-yl)amino)nicotinic acid (NEt-iFQ, 1) exhibits fluorescence solvatochromism, i.e., its Stokes shift depends on the polarity of the solvent, and then we utilized this property to directly measure the internal polarity of the RXRα-LBP. The Stokes shift of 1 when bound to the RXRα-LBP corresponded to that of 1 in chloroform solution. This finding is expected to be helpful for designing RXR-selective ligands. A similar approach should be appliable to evaluate the internal polarity of the LBPs of other receptors.
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キーワード | RXR
Fluorescence
Solvatochromism
Binding assay
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備考 | © 2023 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
This fulltext file will be available in Nov. 2025.
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発行日 | 2023-11-15
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出版物タイトル |
Bioorganic & Medicinal Chemistry Letters
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巻 | 96巻
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出版者 | Elsevier BV
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開始ページ | 129536
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ISSN | 0960-894X
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NCID | AA1079577X
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2023 Elsevier Ltd.
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論文のバージョン | author
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関連URL | isVersionOf https://doi.org/10.1016/j.bmcl.2023.129536
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ライセンス | https://creativecommons.org/licenses/by-nc-nd/4.0/
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助成機関名 |
Okayama Foundation for Science and Technology
Kobayashi Foundation
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