ID | 66178 |
Author |
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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Abstract | 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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Keywords | RXR
Fluorescence
Solvatochromism
Binding assay
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Note | © 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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Published Date | 2023-11-15
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Publication Title |
Bioorganic & Medicinal Chemistry Letters
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Volume | volume96
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Publisher | Elsevier BV
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Start Page | 129536
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ISSN | 0960-894X
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NCID | AA1079577X
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2023 Elsevier Ltd.
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File Version | author
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PubMed ID | |
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Related Url | isVersionOf https://doi.org/10.1016/j.bmcl.2023.129536
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License | https://creativecommons.org/licenses/by-nc-nd/4.0/
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Funder Name |
Okayama Foundation for Science and Technology
Kobayashi Foundation
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