Sunitinib Malate

Sunitinib （Sutent） is a multitargeted FLT3, PDGFRs, VEGFRs, ａnd Kit kinase inhibitor with Ki of 0.009 ａnd 0.008 µM for Flk-1 ａnd PDGFR, respectively. In RS4;11 cells （FLT3-WT）, addition of FL was necessary to stimulate FLT3 phosphorylation, ａnd treatment with SU11248 inhibited FLT3-WT phosphorylation in a dose-dependent manner with a 50% inhibitory concentration of approximately 250 nM. In MV4;11 cells that express FLT3-ITD, it is noteworthy that both high ａnd low molecular weight forms of FLT3 are phosphorylated in the absence of FLT3 ligand （FL）, consistent with expression of FLT3-ITD. Sunitinib Malate （Sutent, SU11248） inhibited FLT3-ITD phosphorylation in a dose-dependent manner with an IC50 of 50 nM following a 2-hour treatment. Evaluating the ability of Sunitinib （Sutent） to inhibit ligand-dependent receptor phosphorylation in cells, the effect of sunitinib （Sutent） on ligand-dependent proliferation of cells was examined. Sunitinib （Sutent） inhibited VEGF- ａnd FGF-induced proliferation of HUVECs with IC50 of 0.04 ａnd 0.7 µM, respectively. Sunitinib （Sutent） also inhibited PDGF-induced proliferation of NIH-3T3 cells overexpressing PDGFRα or PDGFRβ with IC50 of 0.03 ａnd 0.07 µM, respectively. ^[1][2]