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Paradoxical Pro-angiogenic Effect of Low-Dose Ellipticine Identified by In Silico Drug Repurposing
DC Field | Value | Language |
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dc.contributor.author | 오지수 | - |
dc.date.accessioned | 2021-09-29T02:14:48Z | - |
dc.date.available | 2021-09-29T02:14:48Z | - |
dc.date.issued | 2021-08 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/184789 | - |
dc.description.abstract | Inadequate vessel maintenance or growth causes ischemia in diseases such as myocardial infarction, stroke, and neurodegenerative disorders. Therefore, developing an effective strategy to salvage ischemic tissues using a novel compound is urgent. Drug repurposing has become a widely used method that can make drug discovery more efficient and less expensive. Additionally, computational virtual screening tools make drug discovery faster and more accurate. This study found a novel drug candidate for pro-angiogenesis by in silico virtual screening. Using Gene Expression Omnibus (GEO) microarray datasets related to angiogenesis studies, differentially expressed genes were identified and characteristic direction signatures extracted from GEO2EnrichR were used as input data on L1000CDS2 to screen pro-angiogenic molecules. After a thorough review of the candidates, a list of compounds structurally similar to TWS-119 was generated using ChemMine Tools and its clustering toolbox. ChemMine Tools and ChemminR structural similarity search tools for small-molecule analysis and clustering were used for second screening. A molecular docking simulation was conducted using AutoDock v.4 to evaluate the physicochemical effect of secondary-screened chemicals. A cell viability or toxicity test was performed to determine the proper dose of the final candidate, ellipticine. As a result, we found ellipticine, which has pro-angiogenic effects, using virtual computational methods. The noncytotoxic concentration of ellipticine was 156.25 nM. The phosphorylation of glycogen synthase kinase-3β was decreased, whereas the β-catenin expression was increased in human endothelial cells treated with ellipticine. We concluded that ellipticine at sublethal dosage could be successfully repositioned as a pro-angiogenic substance by in silico virtual screening. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.publisher | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Paradoxical Pro-angiogenic Effect of Low-Dose Ellipticine Identified by In Silico Drug Repurposing | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Jisu Oh | - |
dc.contributor.googleauthor | Hyeon Hae Lee | - |
dc.contributor.googleauthor | Yunhui Jeong | - |
dc.contributor.googleauthor | Siyeong Yoon | - |
dc.contributor.googleauthor | Hyun-Ju An | - |
dc.contributor.googleauthor | Minjung Baek | - |
dc.contributor.googleauthor | Do Kyung Kim | - |
dc.contributor.googleauthor | Soonchul Lee | - |
dc.identifier.doi | 10.3390/ijms22169067 | - |
dc.contributor.localId | A06131 | - |
dc.relation.journalcode | J01133 | - |
dc.identifier.eissn | 1422-0067 | - |
dc.identifier.pmid | 34445773 | - |
dc.subject.keyword | angiogenesis | - |
dc.subject.keyword | drug repurposing | - |
dc.subject.keyword | ellipticine | - |
dc.subject.keyword | in silico | - |
dc.subject.keyword | noncytotoxic concentration | - |
dc.contributor.alternativeName | Oh, Jisu | - |
dc.contributor.affiliatedAuthor | 오지수 | - |
dc.citation.volume | 22 | - |
dc.citation.number | 16 | - |
dc.citation.startPage | 9067 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(16) : 9067, 2021-08 | - |
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