Description
As a pan-tyrosine kinase inhibitor, XL-184 (BMS-907351, Cabozantinib) can potently inhibit VEGFR2, Met, Kit, Tie2 and FLT-3 with IC50 of 0.035 nM, 1.8 nM, 4.6 nM, 14.3 nM and 14.4 nM.
Storage
2 years at -20centigrade Powder
Targets
VEGFR2, c-Met, c-Kit, Tie2, FLT-3
Molecular Formula
C28H24FN3O5
Chemical Name
N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Solubility
DMSO 117 mg/mL Water
In vitro
1. Cabozantinib inhibits endothelial cell tubule formation in vitro Cabozantinib inhibited tubule formation with an IC 50 value of 6.7 nmol/L. Cabozantinib also inhibited tubule formation in response to conditioned media derived from cultures of MDA-MB-231 (IC 50 =5.1 nmol/L), A431 (IC 50= 4.1 nmol/L), HT1080 (IC 50 = 7.7 nmol/L), and B16F10 (IC 50 = 4.7 nmol/L) cells. 2. Cabozantinib inhibits cellular migration and invasion Cabozantinib potently inhibited HGF-induced migration (IC 50 = 31 nmol/L) and invasion (IC 50 = 9 nmol/L) of B16F10 cells. VEGF- and HGF-mediated migration of proangiogenic murine MS1 endothelial cells were also sensitive to cabozantinib with IC 50 values of 5.8 and 41 nmol/L.
In vivo
Cabozantinib inhibits MET and VEGFR2 phosphorylation in vivo. A single 100 mg/kg oral dose of cabozantinib resulted in inhibition of phosphorylation of MET 2 to 8 hours postdose in H441 tumors that harbor constitutively phosphorylated MET.
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