A Novel Vascular Endothelial Growth Factor Receptor 2 Inhibitor, SU11248, Suppresses Choroidal Neovascularization<i>In Vivo</i>

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An oral, multitargeted receptor tyrosine kinase inhibitor, SU11248, inhibits vascular endothelial growth factor receptor 2 (VEG FR2, kinase domain receptor F1K1), platelet-derived growth factor receptor, stem cell factor receptor (Kit), and fetal liver tyrosine kinase 3. In this study, we administered SU11248 beyond the completion of an experimental choroidal neovascularization (CNV) model to determine whether CNV growth can be inhibited in vivo.C57B6J mice were treated with daily oral administration (40, 80, and 150 mg/kg) of SU11248 during 5 days after diode laser endophotocoagulation and subjected to angiographic examination and histological analysis.Intensity of fluorescein leakage from the experimental CNV decreased significantly compared to the control eyes. Histological study also revealed that the volume of CNV membrane was significantly reduced in the SU11248-treated eyes.Oral administration of this compound is potentially beneficial in treating CNV caused by age-related macular degeneration (AMD) and other causal diseases. Considering the tolerance the clinical studies for malignant tumors previously demonstrated, further studies to evaluate the clinical efficacy of the drug for AMD might be indicated.

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