223 308

Cited 1 times in

Paradoxical Pro-angiogenic Effect of Low-Dose Ellipticine Identified by In Silico Drug Repurposing

DC Field Value Language
dc.contributor.author오지수-
dc.date.accessioned2021-09-29T02:14:48Z-
dc.date.available2021-09-29T02:14:48Z-
dc.date.issued2021-08-
dc.identifier.issn1661-6596-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/184789-
dc.description.abstractInadequate 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.statementOfResponsibilityopen-
dc.languageINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.publisherINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.relation.isPartOfINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleParadoxical Pro-angiogenic Effect of Low-Dose Ellipticine Identified by In Silico Drug Repurposing-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorJisu Oh-
dc.contributor.googleauthorHyeon Hae Lee-
dc.contributor.googleauthorYunhui Jeong-
dc.contributor.googleauthorSiyeong Yoon-
dc.contributor.googleauthorHyun-Ju An-
dc.contributor.googleauthorMinjung Baek-
dc.contributor.googleauthorDo Kyung Kim-
dc.contributor.googleauthorSoonchul Lee-
dc.identifier.doi10.3390/ijms22169067-
dc.contributor.localIdA06131-
dc.relation.journalcodeJ01133-
dc.identifier.eissn1422-0067-
dc.identifier.pmid34445773-
dc.subject.keywordangiogenesis-
dc.subject.keyworddrug repurposing-
dc.subject.keywordellipticine-
dc.subject.keywordin silico-
dc.subject.keywordnoncytotoxic concentration-
dc.contributor.alternativeNameOh, Jisu-
dc.contributor.affiliatedAuthor오지수-
dc.citation.volume22-
dc.citation.number16-
dc.citation.startPage9067-
dc.identifier.bibliographicCitationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(16) : 9067, 2021-08-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.