{"_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", "download_preview_message": "Download / Preview is available from 2021/9/17.", "file_order": 0, "filename": "CellChemBiol-rev2-Hirota.pdf", "filesize": [{"value": "4.8 MB"}], "format": "application/pdf", "future_date_message": "Download is available from 2021/9/17.", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 4800000.0, "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"], "permalink_uri": "http://hdl.handle.net/2237/00033501", "pubdate": {"attribute_name": "\u516c\u958b\u65e5", "attribute_name_i18n": "\u516c\u958b\u65e5", "attribute_value": "2021-02-09"}, "publish_date": "2021-02-09", "publish_status": "0", "recid": "31321", "relation": {}, "relation_version_is_last": true, "title": ["An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals"], "weko_shared_id": null}