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The small molecule R-(-)-β-O-methylsynephrine binds to nucleoporin 153 kDa and inhibits angiogenesis
Kim N.H.4; Pham N.B.2; Quinn R.J.2; Shim J.S.5; Cho H.4; Cho S.M.4; Park S.W.1; Kim J.H.1; Seok S.H.1; Oh J.-W.4; Kwon H.J.4
2015-07-16
Source PublicationInternational Journal of Biological Sciences
ISSN14492288
Volume11Issue:9Pages:1088-1099
Abstract

R-(-)-β-O-methylsynephrine (OMe-Syn) is a naturally occurring small molecule that was identified in a previous screen as an inhibitor of angiogenesis. In this study, we conducted two animal model experiments to investigate the in vivo antiangiogenic activity of OMe-Syn. OMe-Syn significantly inhibited angiogenesis in a transgenic zebrafish model as well as in a mouse retinopathy model. To elucidate the underlying mechanisms responsible for the antiangiogenic activity of OMe-Syn, we used phage display cloning to isolate potential OMe-Syn binding proteins from human cDNA libraries and identified nucleoporin 153 kDa (NUP153) as a primary binding partner of OMe-Syn. OMe-Syn competitively inhibited mRNA binding to the RNA-binding domain of NUP153. Furthermore, depletion of NUP153 in human cells or zebrafish embryos led to an inhibition of angiogenesis, in a manner similar to that seen in response to OMe-Syn treatment. These data suggest that OMe-Syn is a promising candidate for the development of a novel antiangiogenic agent and that inhibition of NUP153 is possibly responsible for the antiangiogenic activity of OMe-Syn.

KeywordAngiogenesis Natural Product Nup153 Small Molecule Target Identification
DOI10.7150/ijbs.10603
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS SubjectBiochemistry & Molecular Biology ; Biology
WOS IDWOS:000359118900009
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Seoul National University College of Medicine
2.Griffith University
3.Yonsei University College of Medicine
4.Yonsei University
5.Universidade de Macau
Recommended Citation
GB/T 7714
Kim N.H.,Pham N.B.,Quinn R.J.,et al. The small molecule R-(-)-β-O-methylsynephrine binds to nucleoporin 153 kDa and inhibits angiogenesis[J]. International Journal of Biological Sciences,2015,11(9):1088-1099.
APA Kim N.H..,Pham N.B..,Quinn R.J..,Shim J.S..,Cho H..,...&Kwon H.J..(2015).The small molecule R-(-)-β-O-methylsynephrine binds to nucleoporin 153 kDa and inhibits angiogenesis.International Journal of Biological Sciences,11(9),1088-1099.
MLA Kim N.H.,et al."The small molecule R-(-)-β-O-methylsynephrine binds to nucleoporin 153 kDa and inhibits angiogenesis".International Journal of Biological Sciences 11.9(2015):1088-1099.
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