Table 3

SU11248 exhibits dose- and time-dependent inhibition of target RTK phosphorylation and VEGF-induced vascular permeability in vivo

Target modulation studies were performed as described in “Materials and Methods” using mice bearing established A375 (Flk-1/KDR) or SF767T (PDGFRβ) tumors. Data for Flk-1/KDR and PDGFRβ from multiple experiments were combined, and the presence of >50% inhibition relative to vehicle-control animals (based on visual inspection of gels) is indicated. Miles assays to determine inhibition of VEGF-induced vascular permeability were performed as described in “Materials and Methods.” The extent of VEGF-dependent dye leakage from the vasculature into skin was quantified, and the data from three individual mice were combined. The percentage of inhibition relative to vehicle-treated control animals is indicated.

Dose (mg/kg)Duration of inhibition
Target modulationVascular permeability (% Inhibition)
8 h12 h16 h24 h8 h12 h16 h24 h
80YesYesNDaYes95859498
40YesYesNDNo979600
20YesSlightNDNo93004
5NobNoNDNoNDNDNDND
  • a ND, not determined.

  • b Target modulation activity only detected at 4-h timepoint.