3 research outputs found
A novel potent oral series of VEGFR2 inhibitors abrogate tumor growth by inhibiting angiogenesis
This paper describes the identification of 6-(pyrimidin-4-yloxy)-naphthalene-1-carboxamides as a new class of potent and selective human vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitors. In biochemical and cellular assays the compounds exhibit single digit nanomolar potency toward VEGFR2. Compounds of this series show good exposure in rodents when dosed orally. They potently inhibit VEGF-driven angiogenesis in a chamber model and rodent tumor models at daily doses of less than 3 mg/kg by targeting the vasculature as demonstrated by ELISA for TIE-2 in lysates, or by immunohistochemical analysis. This novel series of compounds shows potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role
A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis
This
paper describes the identification of 6-(pyrimidin-4-yloxy)-naphthalene-1-carboxamides
as a new class of potent and selective human vascular endothelial
growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitors. In biochemical
and cellular assays, the compounds exhibit single-digit nanomolar
potency toward VEGFR2. Compounds of this series show good exposure
in rodents when dosed orally. They potently inhibit VEGF-driven angiogenesis
in a chamber model and rodent tumor models at daily doses of less
than 3 mg/kg by targeting the tumor vasculature as demonstrated by
ELISA for TIE-2 in lysates or by immunohistochemical analysis. This
novel series of compounds shows a potential for the treatment of solid
tumors and other diseases where angiogenesis plays an important role