{"created":"2023-07-27T06:51:11.035805+00:00","id":44492,"links":{},"metadata":{"_buckets":{"deposit":"44d7a42c-7fa7-4d52-a991-99fba3c4c154"},"_deposit":{"created_by":18,"id":"44492","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44492"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044492","sets":["2812:2813:2818"]},"author_link":["76362","76363"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-06-10","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"4p.","bibliographicVolumeNumber":"2014-04-01 - 2016-03-31","bibliographic_titles":[{"bibliographic_title":"平成27(2015)年度 科学研究費補助金 若手研究(B) 研究成果報告書"},{"bibliographic_title":"2015 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Fukami, Tatsuki"}],"nameIdentifiers":[{"nameIdentifier":"76363","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"00532300","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=00532300"}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"加水分解反応が毒性発現に関与することが示唆されているものの、未だどの酵素により触媒されるか知られていない医薬品が存在する。本検討では2種の医薬品に注目し、加水分解酵素の同定及び毒性発現への関与を解析した。アセブトロールの副作用としてエリテマトーデスが知られている。ヒトにおいてアセブトロールはカルボキシルエステラーゼ2により効率的に加水分解され、その後にシトクロムP450 2C19により副作用を示す代謝物へ変換されることを明らかにした。ケトコナゾールは経口摂取時の副作用として肝障害が知られており、アリルアセタミドデアセチラーゼによる加水分解反応が毒性発現に重要なステップであることを明らかにした。","subitem_description_type":"Abstract"},{"subitem_description":"In this study, we tried to clarify the identification of esterases responsible for toxicities of two clinical drugs, acebutolol and ketoconazole. Lupus erythematosus and hepatotoxicity are known as side effects of acebutolol and ketoconazole, respectively. We found that acebutolol is hydrolyzed to acetolol by carboxyl esterase (CES) 2, followed by N-hydroxylation of acetolol by Cytochrome P450 (CYP) 2C19. Involvement of this metabolic pathway in acebutolol-induced toxicity was clarified using mice co-administered with CES and P450 inhibitors or inducers by evaluation of anti-nuclear antibody in plasma. Ketoconazole was specifically hydrolyzed to N-deacetylketoconazole by arylacetamide deacetylase (AADAC) in human liver. The involvement of AADAC in ketoconazole-induced toxicity was clarified using human hepatoma HepaRG cells with overexpression of human AADAC. These results would provide useful information for clinical and drug development.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:26860098, 研究期間(年度):2014-04-01 - 2016-03-31","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「薬の副作用発症に関わるオーファン加水分解酵素の機能解析」課題番号26860098\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） \n（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26860098/26860098seika/）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医薬保健研究域薬学系","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00050833","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=00532300"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=00532300","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26860098/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26860098/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26860098/26860098seika/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26860098/26860098seika/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"深見, 達基"}],"nameIdentifiers":[{"nameIdentifier":"76362","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"00532300","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=00532300"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-05-31"}],"displaytype":"detail","filename":"PH-PR-FUKAMI-T-kaken 2016-4p.pdf","filesize":[{"value":"91.1 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"PH-PR-FUKAMI-T-kaken 2016-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44492/files/PH-PR-FUKAMI-T-kaken 2016-4p.pdf"},"version_id":"898b91b7-8b8b-4bda-824c-558f450a829a"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"薬の副作用発症に関わるオーファン加水分解酵素の機能解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"薬の副作用発症に関わるオーファン加水分解酵素の機能解析"},{"subitem_title":"Involvement of orphan esterases in side effects of drugs: acebutolol and ketoconazole","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2818"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-05-31"},"publish_date":"2018-05-31","publish_status":"0","recid":"44492","relation_version_is_last":true,"title":["薬の副作用発症に関わるオーファン加水分解酵素の機能解析"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2024-07-01T05:44:45.911509+00:00"}