Description
E7080 (Lenvatinib) can inhibit VEGFR-2 and VEGFR-3 with IC50 of 4 nM and 5.2 nM.
Storage
2 years at -20 centigrade
Molecular Formula
C21H19ClN4O4
Chemical Name
1-(4-(6-carbamoyl-7-methoxyquinolin-4-yloxy)-2-chlorophenyl)-3-cyclopropylurea
Solubility
DSMO Water Ethanol
In vitro
As an orally active inhibitor of multiple receptor tyrosine kinases, E7080 (Lenvatinib) can inhibit VEGFR-2 and VEGFR-3 with IC50 of 4 nM and 5.2 nM. E7080 (Lenvatinib) also inhibit FGFR, PDGFR and SCFR.(1) H146 cells:Inhibitory activity of E7080 against SCF-induced angiogenesis in vitro and tumor growth of SCF-producing human small cell lung carcinoma H146 cells in vivo. E7080 inhibits SCF-driven tube formation of HUVEC, which express SCF receptor, KIT at the IC50 of 5.2 nM and it was almost identical for VEGF-driven one (IC50 = 5.1 nM).As KIT signaling has a role in tumor angiogenesis of SCF-producing H146 cells, E7080 causes regression of H146 tumors as a result of antiangiogenic activity mediated by inhibition of both KIT and VEGF receptor signaling. (2) MPM cell lines: E7080 potently suppressed the phosphorylation of VEGF receptor-2 and FGF receptor 1 to inhibit proliferation of endothelial cells, but not that of the MPM cell lines, in vitro. Treatment with E7080 potently inhibited the progression of three MPM cell lines (MSTO-211H cells, NCI-H290 and Y-MESO-14 cells) and markedly prolonged mouse survival, which was associated with decreased numbers of tumor-associated vessels and proliferating MPM cells in the tumor.
In vivo
(1) Human sarcoma xenografts. E7080 showed antitumour activity in a dose dependent manner in human sarcoma xenografts. E7080 growth inhibition did not correlate with the expression of VEGFR1-3, PDGFRA, PDGFRB, FGFR1 or KIT on tumour cells but was significantly correlated with expression of VEGFR2 on tumour microvessels. In vitro E7080 did not show potent effects on tumour cell viability in four different sarcoma cell lines, with IC50 values more than 10 uM. (2)MDA-MB-231 and MDA-MB-435 models:E7080 significantly decreased LVD within the MDA-MB-231 tumor. E7080 decreased MVD in both the MDA-MB-231 and MDA-MB-435 models. E7080 significantly suppressed regional lymph nodes and distant lung metastases of MDA-MB-231, E7080 also decreased both MVD and LVD within the metastatic nodules at lymph nodes after resection of the primary tumor. (3) H146 cells: Oral administration of E7080 inhibited tumor growth of H146 cells at doses of 30 and 100 mg/kg in a dose-dependent manner and caused tumor regression at 100 mg/kg.
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