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Development of Nove...
Development of Novel VEGFR2 Inhibitors Originating from Natural Product Analogues with Antiangiogenic Impact
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- Cho, Sung Min (author)
- Yonsei University
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- Kim, Yonghyo (author)
- Lund University,Lunds universitet,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Yonsei University
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- Jung, Yooju (author)
- Yonsei University
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- Ko, Minjeong (author)
- Yonsei University
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- Marko-Varga, Gyorgy (author)
- Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Lund University Research Groups,Yonsei University
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- Kwon, Ho Jeong (author)
- Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups,Yonsei University
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(creator_code:org_t)
- 2021-11-03
- 2021
- English 10 s.
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:21, s. 15858-15867
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Abstract
Subject headings
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- A novel natural small molecule, voacangine (Voa), has been discovered as a potent antiangiogenic compound. Notably, Voa directly binds the kinase domain of the vascular endothelial growth factor receptor 2 (VEGFR2) and thereby inhibits downstream signaling. Herein, we developed synthetic small molecules based on the unique chemical structure of Voa that directly and specifically target and modulate the kinase activity of VEGFR2. Among these Voa structure analogues, Voa analogue 19 (V19) exhibited increased antiangiogenic potency against VEGF-induced VEGFR2 phosphorylation without cytotoxic effects. Moreover, treatment with V19 resulted in significant tumor cell death in a mouse xenograft model. In conclusion, this new VEGFR2 modulator, inspired from the rigid scaffold of a natural compound, Voa, is presented as a potent candidate in the development of new antiangiogenic agents.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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