title: Discovery of N-phenyl nicotinamides as potent inhibitors of Kdr.
abstract: 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.
authors.affiliation: Chemistry Research and Discovery, One Amgen Center Drive Thousand Oaks, CA 91320, USA. celia.dominguez@chdi-inc.org
authors.forename: Celia
authors.initials: C
authors.lastname: Dominguez
authors.forename: Leon
authors.initials: L
authors.lastname: Smith
authors.forename: Qi
authors.initials: Q
authors.lastname: Huang
authors.forename: Chester
authors.initials: C
authors.lastname: Yuan
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Ouyang
authors.forename: Lynn
authors.initials: L
authors.lastname: Cai
authors.forename: Paul
authors.initials: P
authors.lastname: Chen
authors.forename: Joseph
authors.initials: J
authors.lastname: Kim
authors.forename: Timothy
authors.initials: T
authors.lastname: Harvey
authors.forename: Rashid
authors.initials: R
authors.lastname: Syed
authors.forename: Tae-Seong
authors.initials: TS
authors.lastname: Kim
authors.forename: Andrew
authors.initials: A
authors.lastname: Tasker
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Zhang
authors.forename: Angela
authors.initials: A
authors.lastname: Coxon
authors.forename: James
authors.initials: J
authors.lastname: Bready
authors.forename: Charles
authors.initials: C
authors.lastname: Starnes
authors.forename: Danlin
authors.initials: D
authors.lastname: Chen
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Gan
authors.forename: Sesha
authors.initials: S
authors.lastname: Neervannan
authors.forename: Gondi
authors.initials: G
authors.lastname: Kumar
authors.forename: Anthony
authors.initials: A
authors.lastname: Polverino
authors.forename: Richard
authors.initials: R
authors.lastname: Kendall
mesh_terms: 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*
chemical_list: D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D040301:Vascular Endothelial Growth Factor Receptor-2