Structure-Activity Relationship of Indole-Tethered Pyrimidine Derivatives that Concurrently Inhibit Epidermal Growth Factor Receptor and Other Angiokinases
Fig 4
Pazopanib and MKP101 have similar inhibitory effects on VEGF-induced angiogenesis in HUVECs.
(A) Cytotoxicity of pazopanib and MKP101 in HUVECs. No cytotoxicity was observed at 1 μg/mL pazopanib or 1 μg/mL MKP101. (B-D) Pazopanib and MKP101 block VEGF (50 ng/ml)-induced increases in endothelial proliferation (B), tube formation (C), and migration (D). Cell proliferation and tube formation experiments were performed using 1 μg/mL of pazopanib and 1 μg/mL MKP101. The scratch wound migration assay was performed using 0.5 μg/mL pazopanib and 0.5 μg/mL MKP101. In (A) and (B), the number of cells was expressed as the fold change with respect to the number of cells seeded at day 0. Tube formation responses were compared by normalizing the values relative to those of the corresponding PBS control samples (*p < 0.05 vs. PBS; #p < 0.05 vs. VEGF, mean ± SEM). Scale bar = 100 μm.