In vitro VEGFR2 kinase assay, cell proliferation assays, and pharmacokinetic studies

In vitro VEGFR2 kinase assays, human umbilical vein endothelial cell (HUVEC) and MRC5 proliferation assays, and pharmacokinetic studies in Sprague Dawley rats were performed (Pharmaron, Beijing, China). The rats were administered either SU5416 20 mg/kg subcutaneous (SC), cabozantinib 20 mg/kg SC, or cabozantinib 12 mg/kg via an Alzet pump (over seven days). Three rats were studied per group. Plasma samples were obtained at serial timepoints, and SU5416 or cabozantinib were assayed by LC/MSMS.