Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Development of Novel VEGFR2 Inhibitors Originating from Natural Product Analogues with Antiangiogenic Impact

Cho, Sung Min ; Kim, Yonghyo LU ; Jung, Yooju ; Ko, Minjeong ; Marko-Varga, Gyorgy LU and Kwon, Ho Jeong LU (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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
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
2024-06-17 00:44:21
@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}},
}