Cabozantinib

Cabozantinib is a potent and orally active inhibitor of VEGFR2 and MET, with IC₅₀ values of 0.035, and 1.3 nM, respectively. Cabozantinib displays strong inhibition of KIT, RET, AXL, TIE2, and FLT3 (IC₅₀=4.6, 5.2, 7, 14.3, and 11.3 nM, respectively). Cabozantinib shows antiangiogenic activity. Cabozantinib disrupts tumor vasculature and promotes tumor and endothelial cell apoptosis^[1][2]. IC50 & Target:IC₅₀: 0.035 ± 0.01 nM (VEGFR2), 1.3 ± 1.2 nM (MET), 3.8 nM (MET Y1248H), 4.6 ± 0.5 nM (KIT), 7 nM (AXL), 11.3 ± 1.8 nM (FLT3), 11.8 nM (MET D1246N), 14.6 nM (MET K1262R), 124 ± 1.2 nM (RON)^[1] 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^[1].
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^[1].
Cabozantinib (0-370 nM, 24 h) inhibits cellular migration and invasion^[1].
Cabozantinib (48 h) inhibits tumor cell proliferation in a variety of tumor types^[1]. In Vivo:Cabozantinib (100 mg/kg, Orally, once) inhibits MET and VEGFR2 phosphorylation in mice^[1].
Cabozantinib (100 mg/kg, Orally, once) significantly increases tumor hypoxia and apoptosis^[1].
Cabozantinib (0-60 mg/kg, Orally, once daily for 14 days) inhibits tumor growth in a dose-dependent manner^[1].