@article{oai:nagoya.repo.nii.ac.jp:00031321,
 author = {Miller, Simon and Aikawa, Yoshiki and Sugiyama, Akiko and Nagai, Yoshiko and Hara, Aya and Oshima, Tsuyoshi and Amaike, Kazuma and Kay, Steve A. and Itami, Kenichiro and Hirota, Tsuyoshi},
 issue = {9},
 journal = {Cell Chemical Biology},
 month = {Sep},
 note = {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., ファイル公開：2021-09-17},
 pages = {1192--1198.e5},
 title = {An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals},
 volume = {27},
 year = {2020}
}