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Chemical Control of Mammalian Circadian Behavior through Dual Inhibition of Casein Kinase Iα and δ
http://hdl.handle.net/2237/00030455
http://hdl.handle.net/2237/00030455e12ffdf3-b153-4e89-baa8-aaf0ea4c9699
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2019-06-19 | |||||
タイトル | ||||||
タイトル | Chemical Control of Mammalian Circadian Behavior through Dual Inhibition of Casein Kinase Iα and δ | |||||
言語 | en | |||||
著者 |
Lee, Jae Wook
× Lee, Jae Wook× Hirota, Tsuyoshi× Ono, Daisuke× Honma, Sato× Honma, Ken-ichi× Park, Keunwan× Kay, Steve A. |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | “This document is the Accepted Manuscript version of a Published Work that appeared in final form in [Journal of Medicinal Chemistry], copyright © 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].” | |||||
抄録 | ||||||
内容記述 | 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 CKIα and CKIδ dual inhibitors by extensive structural modification of N9 and C2 position of longdaysin. We identified NCC007 that showed stronger period effects (0.32 μM for 5 h period lengthening) in a cell-based circadian assay. The following in vitro kinase assay showed that NCC007 inhibited CKIα and CKIδ with an IC50 of 1.8 and 3.6 μM. 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. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
内容記述 | ||||||
内容記述 | ファイル公開:2020-02-28 | |||||
言語 | ja | |||||
内容記述タイプ | Other | |||||
出版者 | ||||||
言語 | en | |||||
出版者 | ACS Publications | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1021/acs.jmedchem.8b01541 | |||||
ISSN(print) | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0022-2623 | |||||
書誌情報 |
en : Journal of Medicinal Chemistry 巻 62, 号 4, p. 1989-1998, 発行日 2019-02-28 |
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著者版フラグ | ||||||
値 | author |