Journal of Medicinal Chemistry
Article
van de Wouwer, M.; Michaux, C.; Shimada, T.; Jean, I.; Blacher, S.;
Noel, A.; Motte, P.; Rom, E.; Rakic, J. M.; Katsuma, S.; Schaeffer, P.;
Yayon, A.; Van Schepdael, A.; Schwalbe, H.; Gervasio, F. L.; Carmeliet,
G.; Rozensky, J.; Dewerchin, M.; Simons, M.; Christopoulos, A.;
Herbert, J. M.; Carmeliet, P. Inhibition of tumor angiogenesis and
growth by a small-molecule multi-FGF receptor blocker with allosteric
properties. Cancer Cell 2013, 23, 477−488.
Author Contributions
◆N.I.M.-R. and D.A. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by Italfarmaco and grants from the
Spanish Ministerio de Economıa y Competitividad (MINECO,
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(13) Li, D.; Wei, X.; Xie, K.; Chen, K.; Li, J.; Fang, J. A novel decoy
receptor fusion protein for FGF-2 potently inhibits tumour growth. Br.
J. Cancer 2014, 111, 68−77.
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SAF2010-22198, SAF2013-48271, and predoctoral fellowships
to F.J.O.-N., M.B., and S.B.-B.), Instituto de Salud Carlos III
(PI11/00295 and PI14/01101), and Comunidad de Madrid
(S2010/BMD-2353). E.P.-G. is a recipient of a postdoctoral
(14) Wang, Y.; Becker, D. Antisense targeting of basic fibroblast
growth factor and fibroblast growth factor receptor-1 in human
melanomas blocks intratumoral angiogenesis and tumor growth. Nat.
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Christensen, J. G.; Kerbel, R. S. Accelerated metastasis after short-term
treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell
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(16) Loges, S.; Mazzone, M.; Hohensinner, P.; Carmeliet, P.
Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis
revisited. Cancer Cell 2009, 15, 167−170.
(17) Paez-Ribes, M.; Allen, E.; Hudock, J.; Takeda, T.; Okuyama, H.;
Vinals, F.; Inoue, M.; Bergers, G.; Hanahan, D.; Casanovas, O.
Antiangiogenic therapy elicits malignant progression of tumors to
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research contract of the Asociacion Espanola Contra el Cancer.
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The authors thank Campus de Excelencia CEI Moncloa for a
predoctoral fellowship to N.I.M.-R and UCM’s CAI Cytometry
and Fluorescence Microscopy facility for their assistance.
ABBREVIATIONS USED
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bFGF, basic FGF; CSI, chlorosulfonylisocyanate; DIEA, N,N-
diisopropylethylamine; EDC, ethyl-3-(3-(dimethylamino)-
propyl)carbodiimide; FBS, fetal bovine serum; FGFR, FGF
receptor; HIF-1α, hypoxia-inducible factor-1α; HUVECs,
human umbilical vein endothelial cells; SEM, standard error
of the mean; siRNA, small interfering RNA; VEGF, vascular
endothelial growth factor
(19) Philip, B.; Ito, K.; Moreno-Sanchez, R.; Ralph, S. J. HIF
expression and the role of hypoxic microenvironments within primary
tumours as protective sites driving cancer stem cell renewal and
metastatic progression. Carcinogenesis 2013, 34, 1699−1707.
(20) Mole, D. R.; Blancher, C.; Copley, R. R.; Pollard, P. J.; Gleadle,
J. M.; Ragoussis, J.; Ratcliffe, P. J. Genome-wide association of
hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding
with expression profiling of hypoxia-inducible transcripts. J. Biol. Chem.
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