Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis.
RO4396686 is a small molecule KDR, FGFR, and PDGFR inhibitor with good pharmacokinetic properties in rodents. In a mouse corneal neovascularization assay, this compound inhibited VEGF-induced angiogenesis. Tested in a H460a xenograft tumor model this agent effected significant tumor growth inhibition at doses as low as 50mg/kg.
McDermott
Lee A
LA
Hoffmann-La Roche Inc., 340 Kingsland Str., Nutley, NJ 07110-1199, USA. lee.mcdermott@roche.com
Higgins
Brian
B
Simcox
Mary
M
Luk
Kin-Chun
KC
Nevins
Tom
T
Kolinsky
Kenneth
K
Smith
Melissa
M
Yang
Hong
H
Li
Jia K
JK
Chen
Yingsi
Y
Ke
June
J
Mallalieu
Navita
N
Egan
Tom
T
Kolis
Stan
S
Railkar
Aruna
A
Gerber
Louise
L
Liu
Jin-Jun
JJ
Konzelmann
Fred
F
Zhang
Zhuming
Z
Flynn
Tom
T
Morales
Omar
O
Chen
Yi
Y
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D011743:Pyrimidines; C511816:RO4396686; D017468:Receptors, Fibroblast Growth Factor; D042461:Vascular Endothelial Growth Factor A; D017479:Receptors, Platelet-Derived Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2