Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 정수영 | * |
dc.date.accessioned | 2021-08-05T16:31:20Z | - |
dc.date.available | 2021-08-05T16:31:20Z | - |
dc.date.issued | 2021 | * |
dc.identifier.issn | 1424-8247 | * |
dc.identifier.other | OAK-29628 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/258516 | - |
dc.description.abstract | Circadian dysfunction is closely associated with an increased risk of various diseases. Considering that molecular clock machinery serves as an intrinsic time-keeping system underlying the circadian rhythm of biological processes, the modulation of the molecular clock machinery is an at-tractive therapeutic target with novel mechanisms of action. Based on the previous structure–activity relationship study of small molecule cryptochrome (CRY) inhibitors possessing an ethoxypropanoic acid moiety, non-ethoxypropanoic acid-type inhibitors have been developed by bioisosteric replace-ment. They were evaluated as potent and effective enhancers of E-box-mediated transcription, and, in particular, ester 5d and its hydrolysis product 2d exhibited desirable metabolic and pharmacokinetic profiles as promising drug candidates. Compound 2d directly bound to both CRY1 and 2 in surface plasmon resonance analyses, suggesting that the molecular target is CRY. Effects of compound 5d and 2d on suppressive action of CRY1 on CLOCK:BMAL1-activated E-box-LUC reporter activity revealed that both compounds inhibited the negative feedback actions of CRY on CLOCK:BMAL1. Most importantly, compounds 5d and 2d exhibited significant effects on molecular circadian rhythmicity to be considered circadian clock-enhancers, distinct from the previously developed CRY inhibitors possessing an ethoxypropanoic acid moiety. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. | * |
dc.language | English | * |
dc.publisher | MDPI AG | * |
dc.subject | Bioisosteric replacement | * |
dc.subject | Circadian clock | * |
dc.subject | Circadian rhythm | * |
dc.subject | Cryptochrome inhibitor | * |
dc.title | Development of non-ethoxypropanoic acid type cryptochrome inhibitors with circadian molecular clock-enhancing activity by bioisosteric replacement | * |
dc.type | Article | * |
dc.relation.issue | 6 | * |
dc.relation.volume | 14 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | Pharmaceuticals | * |
dc.identifier.doi | 10.3390/ph14060496 | * |
dc.identifier.wosid | WOS:000666776000001 | * |
dc.identifier.scopusid | 2-s2.0-85107494479 | * |
dc.author.google | Jeong Y.U. | * |
dc.author.google | Jin H.-E. | * |
dc.author.google | Lim H.Y. | * |
dc.author.google | Choi G. | * |
dc.author.google | Joo H. | * |
dc.author.google | Kang B. | * |
dc.author.google | Lee G.-H. | * |
dc.author.google | Liu K.-H. | * |
dc.author.google | Maeng H.-J. | * |
dc.author.google | Chung S. | * |
dc.author.google | Son G.H. | * |
dc.author.google | Jung J.-W. | * |
dc.contributor.scopusid | 정수영(7404292716) | * |
dc.date.modifydate | 20231123124347 | * |