Lenvatinib (E7080) is a multitargeted kinase inhibitor with IC50s of 4/5.2/22/46 nM for VEGFR2/VEGFR3/VEGFR1/FGFR1 in cell free assays.
Description :
Lenvatinib (E7080) is a multitargeted kinase inhibitor with IC50s of 4/5.2/22/46 nM for VEGFR2/VEGFR3/VEGFR1/FGFR1 in cell free assays; also inhibits PDGFR, Kit with IC50< 100 nM; suppresses the phosphorylation of VEGF receptor-2 and FGF receptor 1 and inhibits proliferation of endothelial cellin vitro; orally active.
Kidney Cancer
E7080, as a potent inhibitor of in vitro angiogenesis, shows a significantly inhibitory effect on VEGF/KDR and SCF/Kit signaling. According to the in vitro receptor tyrosine and serine/threonine kinase assays, E7080 inhibits Flt-1, KDR, Flt-4 with IC50 of 22, 4.0 and 5.2 nM, respectively. In addition to these kinases, E7080 also inhibits FGFR1 and PDGFR tyrosine kinases with IC50 value of 46, 51 and 100 nM for FGFR1, PDGFRα and PDGFRβ, respectively. [1] E7080 potently inhibits phosphorylation of VEGFR2 (IC50, 0.83 nM) and VEGFR3 (IC50, 0.36 nM) in HUVECs which is stimulated by VEGF and VEGF-C, respectively. [2] A recent study shows that E7080 treatment (both at 1 μM and 10 μM) results in a significant inhibition of cell migration and invasion by inhibiting FGFR and PDGFR signaling. [3]
Lenvatinib inhibits the growth of H146 tumor at 30 and 100 mg/kg (BID, QDx21) in a dose-dependent manner and causes tumor regression at 100 mg/kg in H146 xenograft model. IHC analysis with anti-CD31 antibody shows that lenvatinib at 100 mg/kg decreases microvessel density more than anti-VEGF antibody and imatinib treatment[1]. lenvatinib (100 mg/kg, p.o.) is administeredand bevacizumab significantly inhibits local tumor growth at the m.f.p., and at the end of treatment, lenvatinib also significantly inhibits metastasis to both regional lymph nodes and distant lung[2].