Development of Novel VEGFR2 Inhibitors Originating from Natural Product Analogues with Antiangiogenic Impact
(2021) In Journal of Medicinal Chemistry 64(21). p.15858-15867- Abstract
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,... (More)
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.
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- author
- Cho, Sung Min ; Kim, Yonghyo LU ; Jung, Yooju ; Ko, Minjeong ; Marko-Varga, Gyorgy LU and Kwon, Ho Jeong LU
- organization
- publishing date
- 2021-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Medicinal Chemistry
- volume
- 64
- issue
- 21
- pages
- 10 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:85119037498
- pmid:34730352
- ISSN
- 0022-2623
- DOI
- 10.1021/acs.jmedchem.1c01168
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 American Chemical Society.
- id
- 95dbb9d9-f22b-4209-b5df-abcf0976ad86
- date added to LUP
- 2021-12-03 08:37:54
- date last changed
- 2024-09-22 07:02:59
@article{95dbb9d9-f22b-4209-b5df-abcf0976ad86, abstract = {{<p>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.</p>}}, author = {{Cho, Sung Min and Kim, Yonghyo and Jung, Yooju and Ko, Minjeong and Marko-Varga, Gyorgy and Kwon, Ho Jeong}}, issn = {{0022-2623}}, language = {{eng}}, number = {{21}}, pages = {{15858--15867}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Journal of Medicinal Chemistry}}, title = {{Development of Novel VEGFR2 Inhibitors Originating from Natural Product Analogues with Antiangiogenic Impact}}, url = {{http://dx.doi.org/10.1021/acs.jmedchem.1c01168}}, doi = {{10.1021/acs.jmedchem.1c01168}}, volume = {{64}}, year = {{2021}}, }