Indirubin-3 '-alkoxime derivatives for upregulation of Wnt signaling through dual inhibition of GSK-3 beta and the CXXC5-Dvl interaction
DC Field | Value | Language |
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dc.contributor.author | Song, Doona | - |
dc.contributor.author | Lee, Yunja | - |
dc.contributor.author | Kang, Min-Jeong | - |
dc.contributor.author | Kim, Jae Won | - |
dc.contributor.author | Lee, Soung-Hoon | - |
dc.contributor.author | Choi, Kang-Yell | - |
dc.contributor.author | Kim, Eun-Yeong | - |
dc.contributor.author | Lee, Kiho | - |
dc.contributor.author | Han, Gyoonhee | - |
dc.date.accessioned | 2022-08-14T04:40:18Z | - |
dc.date.available | 2022-08-14T04:40:18Z | - |
dc.date.created | 2022-08-12 | - |
dc.date.issued | 2022-04 | - |
dc.identifier.issn | 0045-2068 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/143109 | - |
dc.description.abstract | Glycogen synthase kinase-3 beta (GSK-3 beta) appears to be ordinarily expressed, and functionally redundant in Wnt/ beta-catenin signaling. The Wnt proteins induce transduction of a cytoplasmic protein, Dishevelled (Dvl) which negatively modulates GSK-3 beta activity. CXXC5 is a negative modulator of the Wnt/beta-catenin signaling through the interaction with Dvl in the cytosol. This indicates that Wnt/beta-catenin signaling could be efficiently modulated by controlling GSK-3 beta and the CXXC5-Dvl interaction. In this study, we designed a series of indirubin-3 & PRIME;-oxime and indirubin-3'-alkoxime derivatives containing various functional groups at the 5-or 6-position (R-1) alongside alkyl or benzylic moieties at the 3'-oxime position (R-2). These activate Wnt signaling through inhibitions of both GSK-3 beta and the CXXC5-Dvl protein-protein interaction, in addition, the improvement of pharmacological properties. The potent activity profiles of the synthesized compounds suggested that dual inhibition of GSK-3 beta and the CXXC5-Dvl interaction could be an appropriate approach towards safely and efficiently activating Wnt signaling. Thus, dual-targeting inhibitors are potentially better candidates for efficient activation of Wnt -signaling compared to GSK-3 beta inhibitors. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.subject | WNT/BETA-CATENIN | - |
dc.subject | BETA-CATENIN | - |
dc.subject | PDZ DOMAIN | - |
dc.subject | PATHWAY | - |
dc.subject | STABILITY | - |
dc.subject | DISEASE | - |
dc.title | Indirubin-3 '-alkoxime derivatives for upregulation of Wnt signaling through dual inhibition of GSK-3 beta and the CXXC5-Dvl interaction | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Kiho | - |
dc.identifier.doi | 10.1016/j.bioorg.2022.105664 | - |
dc.identifier.scopusid | 2-s2.0-85124572934 | - |
dc.identifier.wosid | 000788722400001 | - |
dc.identifier.bibliographicCitation | BIOORGANIC CHEMISTRY, v.121 | - |
dc.relation.isPartOf | BIOORGANIC CHEMISTRY | - |
dc.citation.title | BIOORGANIC CHEMISTRY | - |
dc.citation.volume | 121 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Organic | - |
dc.subject.keywordPlus | WNT/BETA-CATENIN | - |
dc.subject.keywordPlus | BETA-CATENIN | - |
dc.subject.keywordPlus | PDZ DOMAIN | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | STABILITY | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordAuthor | Indirubin-3 &apos | - |
dc.subject.keywordAuthor | -alkoxime derivatives | - |
dc.subject.keywordAuthor | Wnt signaling | - |
dc.subject.keywordAuthor | GSK-3 beta | - |
dc.subject.keywordAuthor | CXXC5-Dvl interaction | - |
dc.subject.keywordAuthor | Dual inhibition | - |
dc.subject.keywordAuthor | Wound healing | - |
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