{"created":"2021-03-01T06:36:19.765672+00:00","id":28259,"links":{},"metadata":{"_buckets":{"deposit":"c2b5eb11-5de0-43c7-af78-aba3f8671860"},"_deposit":{"id":"28259","owners":[],"pid":{"revision_id":0,"type":"depid","value":"28259"},"status":"published"},"_oai":{"id":"oai:nagoya.repo.nii.ac.jp:00028259"},"item_10_biblio_info_6":{"attribute_name":"\u66f8\u8a8c\u60c5\u5831","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-02-28","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4","bibliographicPageEnd":"1998","bibliographicPageStart":"1989","bibliographicVolumeNumber":"62","bibliographic_titles":[{"bibliographic_title":"Journal of Medicinal Chemistry"}]}]},"item_10_description_4":{"attribute_name":"\u6284\u9332","attribute_value_mlt":[{"subitem_description":"Circadian rhythms are controlled by transcriptional feedback loops of clock genes and proteins. The stability of clock proteins is regulated by post-translational modification, such as phosphorylation by kinases. In particular, casein kinase I (CKI) phosphorylates the PER protein to regulate proteasomal degradation and nuclear localization. Therefore, CKI inhibition can modulate mammalian circadian rhythms. In the present study, we have developed novel CKI\u03b1 and CKI\u03b4 dual inhibitors by extensive structural modification of N9 and C2 position of longdaysin. We identified NCC007 that showed stronger period effects (0.32 \u03bcM for 5 h period lengthening) in a cell-based circadian assay. The following in vitro kinase assay showed that NCC007 inhibited CKI\u03b1 and CKI\u03b4 with an IC50 of 1.8 and 3.6 \u03bcM. We further demonstrated that NCC007 lengthened the period of mouse behavioral rhythms in vivo. Thus, NCC007 is a valuable tool compound to control circadian rhythms through CKI inhibition.","subitem_description_type":"Abstract"}]},"item_10_description_5":{"attribute_name":"\u5185\u5bb9\u8a18\u8ff0","attribute_value_mlt":[{"subitem_description":"\u30d5\u30a1\u30a4\u30eb\u516c\u958b\uff1a2020-02-28","subitem_description_type":"Other"}]},"item_10_publisher_32":{"attribute_name":"\u51fa\u7248\u8005","attribute_value_mlt":[{"subitem_publisher":"ACS Publications"}]},"item_10_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1021/acs.jmedchem.8b01541","subitem_relation_type_select":"DOI"}}]},"item_10_rights_12":{"attribute_name":"\u6a29\u5229","attribute_value_mlt":[{"subitem_rights":"\u201cThis document is the Accepted Manuscript version of a Published Work that appeared in final form in [Journal of Medicinal Chemistry], copyright \u00a9 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [https://pubs.acs.org/articlesonrequest/AOR-qexwhhQMVnBfF65bRRm8].\u201d "}]},"item_10_select_15":{"attribute_name":"\u8457\u8005\u7248\u30d5\u30e9\u30b0","attribute_value_mlt":[{"subitem_select_item":"author"}]},"item_10_source_id_61":{"attribute_name":"ISSN\uff08print\uff09","attribute_value_mlt":[{"subitem_source_identifier":"0022-2623","subitem_source_identifier_type":"ISSN"}]},"item_creator":{"attribute_name":"\u8457\u8005","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Lee, Jae Wook"}],"nameIdentifiers":[{"nameIdentifier":"92191","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hirota, Tsuyoshi"}],"nameIdentifiers":[{"nameIdentifier":"92192","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ono, Daisuke"}],"nameIdentifiers":[{"nameIdentifier":"92193","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Honma, Sato"}],"nameIdentifiers":[{"nameIdentifier":"92194","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Honma, Ken-ichi"}],"nameIdentifiers":[{"nameIdentifier":"92195","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Park, Keunwan"}],"nameIdentifiers":[{"nameIdentifier":"92196","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kay, Steve A."}],"nameIdentifiers":[{"nameIdentifier":"92197","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"\u30d5\u30a1\u30a4\u30eb\u60c5\u5831","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-02-28"}],"displaytype":"detail","filename":"Jee-Hirota-JMC-final.pdf","filesize":[{"value":"1.6 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Jee-Hirota-JMC-final","url":"https://nagoya.repo.nii.ac.jp/record/28259/files/Jee-Hirota-JMC-final.pdf"},"version_id":"095bc3b9-c6e3-46c4-a48a-950805dcc179"}]},"item_language":{"attribute_name":"\u8a00\u8a9e","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"\u8cc7\u6e90\u30bf\u30a4\u30d7","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Chemical Control of Mammalian Circadian Behavior through Dual Inhibition of Casein Kinase I\u03b1 and \u03b4","item_titles":{"attribute_name":"\u30bf\u30a4\u30c8\u30eb","attribute_value_mlt":[{"subitem_title":"Chemical Control of Mammalian Circadian Behavior through Dual Inhibition of Casein Kinase I\u03b1 and \u03b4"}]},"item_type_id":"10","owner":"1","path":["1935/1936/1937"],"pubdate":{"attribute_name":"\u516c\u958b\u65e5","attribute_value":"2019-06-19"},"publish_date":"2019-06-19","publish_status":"0","recid":"28259","relation_version_is_last":true,"title":["Chemical Control of Mammalian Circadian Behavior through Dual Inhibition of Casein Kinase I\u03b1 and \u03b4"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2021-03-01T10:15:27.980597+00:00"}