| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-07-09 |
| タイトル |
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タイトル |
Scaffold-Hopped Compound Identification by Ligand-Based Approaches with a Prospective Affinity Test |
| 言語 |
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言語 |
eng |
| キーワード |
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主題Scheme |
Other |
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主題 |
Biological databases |
| キーワード |
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主題Scheme |
Other |
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主題 |
Color |
| キーワード |
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主題Scheme |
Other |
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主題 |
Molecular structure |
| キーワード |
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主題Scheme |
Other |
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主題 |
Molecules |
| キーワード |
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主題Scheme |
Other |
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主題 |
Scaffolds |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Maeda, Itsuki
Tamura, Shunsuke
Ogura, Yoshihiro
Serizawa, Takayuki
Shimada, Takashi
Kunimoto, Ryo
宮尾, 知幸
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Scaffold-hopped (SH) compounds are bioactive compounds structurally different from known active compounds. Identifying SH compounds in the ligand-based approaches has been a central issue in medicinal chemistry, and various molecular representations of scaffold hopping have been proposed. However, appropriate representations for SH compound identification remain unclear. Herein, the ability of SH compound identification among several representations was fairly evaluated based on retrospective validation and prospective demonstration. In the retrospective validation, the combinations of two screening algorithms and four two- and three-dimensional molecular representations were compared using controlled data sets for the early identification of SH compounds. We found that the combination of the support vector machine and extended connectivity fingerprint with bond diameter 4 (SVM-ECFP4) and SVM and the rapid overlay of chemical structures (SVM-ROCS) showed a relatively high performance. The compounds that were highly ranked by SVM-ROCS did not share substructures with the active training compounds, while those ranked by SVM-ECFP4 were mostly recombinant. In the prospective demonstration, 93 SH compounds were prepared by screening the Namiki database using SVM-ROCS, targeting ABL1 inhibitors. The primary screening using surface plasmon resonance suggested five active compounds; however, in the competitive binding assays with adenosine triphosphate, no hits were found. |
| 書誌情報 |
en : Journal of Chemical Information and Modeling
巻 64,
号 14,
p. 5557-5569,
ページ数 13,
発行日 2024-07-22
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| 出版者 |
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出版者 |
American Chemical Society |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1549-960X |
| 出版者版DOI |
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関連タイプ |
isReplacedBy |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1021/acs.jcim.4c00342 |
| 出版者版URI |
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関連タイプ |
isReplacedBy |
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識別子タイプ |
URI |
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関連識別子 |
https://pubs.acs.org/doi/10.1021/acs.jcim.4c00342 |
| 権利 |
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権利情報Resource |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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権利情報 |
$00A9 2024 The Authors. Published by American Chemical Society. This article is licensed under CC-BY-NC-ND 4.0 |
| 著者版フラグ |
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出版タイプ |
NA |
