1.
Bioorg Med Chem Lett
; 16(7): 1950-3, 2006 Apr 01.
Article
in English
| MEDLINE
| ID: mdl-16460940
ABSTRACT
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.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Neoplasms, Experimental/blood supply , Neovascularization, Pathologic , Pyrimidines/pharmacology , Angiogenesis Inhibitors/chemistry , Animals , Mice , Mice, Nude , Rats , Rats, Wistar , Receptors, Fibroblast Growth Factor/antagonists & inhibitors , Receptors, Platelet-Derived Growth Factor/antagonists & inhibitors , Vascular Endothelial Growth Factor A/physiology , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
2.
Bioorg Med Chem
; 13(16): 4835-41, 2005 Aug 15.
Article
in English
| MEDLINE
| ID: mdl-15953730
ABSTRACT
(+/-)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR. This agent has an excellent pharmacokinetic profile and is highly efficacious in rodent models of angiogenesis upon oral administration.
