Discovery of N-phenyl nicotinamides as potent inhibitors of Kdr.
Inhibition of tumor-induced angiogenesis is a promising strategy in anticancer research. Neovascularization is a process required for both tumor growth and metastasis. Enhanced understanding of the underlying molecular mechanisms has led to the discovery of a variety of pharmaceutically attractive targets. Decades of investigation suggest that vascular endothelial growth factor (VEGF) and its receptors, in particular VEGFR2 or kinase insert-domain-containing receptor (Kdr), play a critical role in the growth and survival of endothelial cells in newly forming vasculature. The clinical utility of inhibitors of this receptor tyrosine kinase is currently under intense investigation. Herein we report our efforts in this arena.
Dominguez
Celia
C
Chemistry Research and Discovery, One Amgen Center Drive Thousand Oaks, CA 91320, USA. celia.dominguez@chdi-inc.org
Smith
Leon
L
Huang
Qi
Q
Yuan
Chester
C
Ouyang
Xiaohu
X
Cai
Lynn
L
Chen
Paul
P
Kim
Joseph
J
Harvey
Timothy
T
Syed
Rashid
R
Kim
Tae-Seong
TS
Tasker
Andrew
A
Wang
Ling
L
Zhang
Michael
M
Coxon
Angela
A
Bready
James
J
Starnes
Charles
C
Chen
Danlin
D
Gan
Yongmei
Y
Neervannan
Sesha
S
Kumar
Gondi
G
Polverino
Anthony
A
Kendall
Richard
R
D045744:Cell Line, Tumor; D006801:Humans; D009536:Niacinamide / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D040301:Vascular Endothelial Growth Factor Receptor-2