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薬の副作用発現に関与するヒト還元酵素の同定および機能解析
https://doi.org/10.24517/00054515
https://doi.org/10.24517/00054515f5991120-a653-4ef2-a426-6ff961329498
名前 / ファイル | ライセンス | アクション |
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PH-PR-FUKAMI-T-kaken 2019-4p.pdf (90.7 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2020-04-23 | |||||
タイトル | ||||||
タイトル | 薬の副作用発現に関与するヒト還元酵素の同定および機能解析 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Elucidation of reductases related with side effects of clinical drugs | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
資源タイプ | research report | |||||
ID登録 | ||||||
ID登録 | 10.24517/00054515 | |||||
ID登録タイプ | JaLC | |||||
著者 |
深見, 達基
× 深見, 達基 |
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著者別表示 |
Fukami, Tatsuki
× Fukami, Tatsuki |
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書誌情報 |
平成30(2018)年度 科学研究費補助金 基盤研究(C) 研究成果報告書 en : 2018 Fiscal Year Final Research Report 巻 2016-04-01 - 2019-03-31, p. 4p., 発行日 2019-05-23 |
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出版者 | ||||||
出版者 | 金沢大学医薬保健研究域薬学系 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | ニトロ基の還元反応が肝障害などの副作用に関連することが示唆されていたニトラゼパムの還元酵素をヒト肝臓より精製した結果、アルデヒドオキシダーゼ 1(AOX1)が単離された。また、本酵素の還元酵素活性は生体内物質N-メチルニコチンアミド存在下で著しく上昇した。還元反応の中間体として不安定であるN-ヒドロキシアミンが生成することを明らかにし、これが副作用発現に関与することが示唆された。AOX1がどのようなニトロ基含有医薬品を還元するのか解析した結果、ダントロレンやフルタミドなど、ニトロ基の電子密度が比較的低く、臨床で還元体生成が認められ、かつ肝障害が副作用として報告されているものが該当した。 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Enzyme responsible for reduction of nitrazepam, which causes hepatotoxicity as a side effect, was purified from human liver, resulting in the isolation of aldehyde oxidase 1 (AOX1). Nitrazepam reductase activity was enhanced in the presence of N-methylnicotinamide, which is an endogenous substrate of AOX1. In the process of reduction, nitrazepam was converted to N-hydroxyl amine form, which has been accepted to related with several toxicity because of its instability. This unstable intermediate may cause hepatotoxicity by nitrazepam. It was investigated which compounds were reduced by AOX1 in human, resulting that some compounds reported to cause hepatotoxicity as a side effect, including dantrolene and flutamide, were reduced by AOX1. Common characteristics among them were to possess relatively electron-deficient nitro group. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 研究課題/領域番号:16K08367, 研究期間(年度):2016-04-01 - 2019-03-31 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 出典:研究課題「薬の副作用発現に関与するヒト還元酵素の同定および機能解析」課題番号16K08367 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) (https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-16K08367/16K08367seika/)を加工して作成 |
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著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/search/?qm=00532300 | |||||
関連名称 | https://kaken.nii.ac.jp/search/?qm=00532300 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K08367/ | |||||
関連名称 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K08367/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-16K08367/16K08367seika/ | |||||
関連名称 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-16K08367/16K08367seika/ |