{"created":"2021-03-01T06:39:44.207682+00:00","id":31321,"links":{},"metadata":{"_buckets":{"deposit":"653a6674-33a3-414f-81a2-2381e6ffb53c"},"_deposit":{"id":"31321","owners":[],"pid":{"revision_id":0,"type":"depid","value":"31321"},"status":"published"},"_oai":{"id":"oai:nagoya.repo.nii.ac.jp:00031321"},"item_10_biblio_info_6":{"attribute_name":"\u66f8\u8a8c\u60c5\u5831","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-09-17","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"9","bibliographicPageEnd":"1198.e5","bibliographicPageStart":"1192","bibliographicVolumeNumber":"27","bibliographic_titles":[{"bibliographic_title":"Cell Chemical Biology"}]}]},"item_10_description_4":{"attribute_name":"\u6284\u9332","attribute_value_mlt":[{"subitem_description":"Cryptochrome 1 (CRY1) and CRY2 are core regulators of the circadian clock, and the development of isoform-selective modulators is important for the elucidation of their redundant and distinct functions. Here, we report the identification and functional characterization of a small-molecule modulator of the mammalian circadian clock that selectively controls CRY1. Cell-based circadian chemical screening identified a thienopyrimidine derivative KL201 that lengthened the period of circadian rhythms in cells and tissues. Functional assays revealed stabilization of CRY1 but not CRY2 by KL201. A structure-activity relationship study of KL201 derivatives in combination with X-ray crystallography of the CRY1-KL201 complex uncovered critical sites and interactions required for CRY1 regulation. KL201 bound to CRY1 in overlap with FBXL3, a subunit of ubiquitin ligase complex, and the effect of KL201 was blunted by knockdown of FBXL3. KL201 will facilitate isoform-selective regulation of CRY1 to accelerate chronobiology research and therapeutics against clock-related diseases.","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\uff1a2021-09-17","subitem_description_type":"Other"}]},"item_10_publisher_32":{"attribute_name":"\u51fa\u7248\u8005","attribute_value_mlt":[{"subitem_publisher":"Elsevier"}]},"item_10_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.chembiol.2020.05.008","subitem_relation_type_select":"DOI"}}]},"item_10_rights_12":{"attribute_name":"\u6a29\u5229","attribute_value_mlt":[{"subitem_rights":"\u00a9 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/"}]},"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":"2451-9456","subitem_source_identifier_type":"ISSN"}]},"item_creator":{"attribute_name":"\u8457\u8005","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Miller, Simon"}],"nameIdentifiers":[{"nameIdentifier":"103360","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Aikawa, Yoshiki"}],"nameIdentifiers":[{"nameIdentifier":"103361","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sugiyama, Akiko"}],"nameIdentifiers":[{"nameIdentifier":"103362","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nagai, Yoshiko"}],"nameIdentifiers":[{"nameIdentifier":"103363","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hara, Aya"}],"nameIdentifiers":[{"nameIdentifier":"103364","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Oshima, Tsuyoshi"}],"nameIdentifiers":[{"nameIdentifier":"103365","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Amaike, Kazuma"}],"nameIdentifiers":[{"nameIdentifier":"103366","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kay, Steve A."}],"nameIdentifiers":[{"nameIdentifier":"103367","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Itami, Kenichiro"}],"nameIdentifiers":[{"nameIdentifier":"103368","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hirota, Tsuyoshi"}],"nameIdentifiers":[{"nameIdentifier":"103369","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":"2021-09-17"}],"displaytype":"detail","filename":"CellChemBiol-rev2-Hirota.pdf","filesize":[{"value":"4.8 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"CellChemBiol-rev2-Hirota","url":"https://nagoya.repo.nii.ac.jp/record/31321/files/CellChemBiol-rev2-Hirota.pdf"},"version_id":"704857f2-c370-4bae-9d58-51d34a8120c7"}]},"item_keyword":{"attribute_name":"\u30ad\u30fc\u30ef\u30fc\u30c9","attribute_value_mlt":[{"subitem_subject":"circadian clock","subitem_subject_scheme":"Other"},{"subitem_subject":"cryptochrome","subitem_subject_scheme":"Other"},{"subitem_subject":"small-molecule modulator","subitem_subject_scheme":"Other"},{"subitem_subject":"chemical biology","subitem_subject_scheme":"Other"},{"subitem_subject":"X-ray crystallography","subitem_subject_scheme":"Other"}]},"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":"An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals","item_titles":{"attribute_name":"\u30bf\u30a4\u30c8\u30eb","attribute_value_mlt":[{"subitem_title":"An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals"}]},"item_type_id":"10","owner":"1","path":["1935/1936/1937"],"pubdate":{"attribute_name":"\u516c\u958b\u65e5","attribute_value":"2021-02-09"},"publish_date":"2021-02-09","publish_status":"0","recid":"31321","relation_version_is_last":true,"title":["An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2021-03-01T08:28:00.574695+00:00"}