Rational discovery of antimetastatic agents targeting the intrinsically disordered region of MBD2
DC Field | Value | Language |
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dc.contributor.author | Kim, Min Young | - |
dc.contributor.author | Na, Insung | - |
dc.contributor.author | Kim, Ji Sook | - |
dc.contributor.author | Son, Seung Han | - |
dc.contributor.author | Choi, Sungwoo | - |
dc.contributor.author | Lee, Seol Eui | - |
dc.contributor.author | Kim, Ji-Hun | - |
dc.contributor.author | Jang, Kiseok | - |
dc.contributor.author | Alterovitz, Gil | - |
dc.contributor.author | Chen, Yu | - |
dc.contributor.author | van der Vaart, Arjan | - |
dc.contributor.author | Won, Hyung-Sik | - |
dc.contributor.author | Uversky, Vladimir N. | - |
dc.contributor.author | Kim, Chul Geun | - |
dc.date.accessioned | 2021-08-02T10:51:12Z | - |
dc.date.available | 2021-08-02T10:51:12Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2019-11 | - |
dc.identifier.issn | 2375-2548 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/12337 | - |
dc.description.abstract | Although intrinsically disordered protein regions (IDPRs) are commonly engaged in promiscuous protein-protein interactions (PPIs), using them as drug targets is challenging due to their extreme structural flexibility. We report a rational discovery of inhibitors targeting an IDPR of MBD2 that undergoes disorder-to-order transition upon PPI and is critical for the regulation of the Mi-2/NuRD chromatin remodeling complex (CRC). Computational biology was essential for identifying target site, searching for promising leads, and assessing their binding feasibility and off-target probability. Molecular action of selected leads inhibiting the targeted PPI of MBD2 was validated in vitro and in cell, followed by confirming their inhibitory effects on the epithelial-mesenchymal transition of various cancer cells. Identified lead compounds appeared to potently inhibit cancer metastasis in a murine xenograft tumor model. These results constitute a pioneering example of rationally discovered IDPR-targeting agents and suggest Mi-2/NuRD CRC and/or MBD2 as a promising target for treating cancer metastasis. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | - |
dc.title | Rational discovery of antimetastatic agents targeting the intrinsically disordered region of MBD2 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jang, Kiseok | - |
dc.contributor.affiliatedAuthor | Kim, Chul Geun | - |
dc.identifier.doi | 10.1126/sciadv.aav9810 | - |
dc.identifier.scopusid | 2-s2.0-85074586864 | - |
dc.identifier.wosid | 000499736100009 | - |
dc.identifier.bibliographicCitation | SCIENCE ADVANCES, v.5, no.11, pp.2375 - 2548 | - |
dc.relation.isPartOf | SCIENCE ADVANCES | - |
dc.citation.title | SCIENCE ADVANCES | - |
dc.citation.volume | 5 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 2375 | - |
dc.citation.endPage | 2548 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | COILED-COIL INTERACTION | - |
dc.subject.keywordPlus | PARTICLE MESH EWALD | - |
dc.subject.keywordPlus | MOLECULAR-DYNAMICS | - |
dc.subject.keywordPlus | PROTEIN-PROTEIN | - |
dc.subject.keywordPlus | CPG ISLANDS | - |
dc.subject.keywordPlus | MYC-MAX | - |
dc.subject.keywordPlus | C-MYC | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | PARALLEL | - |
dc.subject.keywordPlus | COMPLEX | - |
dc.identifier.url | https://www.science.org/doi/10.1126/sciadv.aav9810 | - |
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