Cabozantinib

Cabozantinib (XL184, BMS-907351) is a potent multi-kinase inhibitor that inhibits VEGFR2, c-Met, Kit, Axl and Flt3 with IC50 of 0.035, 1.3, 4.6, 7 and 11.3 nM, respectively; eliminates tumor vasculature, reduces pericytes and empty basement membrane sleeves, causes widespread intratumoral hypoxia and tumor cell apoptosis, and slows regrowth of the tumor vasculature, also decreases invasiveness of primary tumors and reduces metastasis in pancreatic islet cancer; exerts marked anti-MPNST effects in vitro and in vivo.Kidney Cancer Approved (In Vitro) :Cabozantinib inhibits phosphorylation of MET and VEGFR2, as well as KIT, FLT3, and AXL with IC50 values of 7.8, 1.9, 5.0, 7.5, and 42 μM, respectively.Cabozantinib (4.6 nM) inhibits tubule formation with no evidence of cytotoxicity, with IC50 values of 6.7, 5.1, 4.1, 7.7, and 4.7 nM in HMVEC, MDA-MB-231, A431, HT1080, and B16F10 cells, respectively.Cabozantinib (0-370 nM, 24 h) inhibits cellular migration and invasion.Cabozantinib (48 h) inhibits tumor cell proliferation in a variety of tumor types. (In Vivo) :Cabozantinib (100 mg/kg, Orally, once) inhibits MET and VEGFR2 phosphorylation in mice.Cabozantinib (100 mg/kg, Orally, once) significantly increases tumor hypoxia and apoptosis.Cabozantinib (0-60 mg/kg, Orally, once daily for 14 days) inhibits tumor growth in a dose-dependent manner.