tcsc0109 Lenvatinib

Lenvatinib is an orally active, multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC₅₀ of 4 nM/5.2 nM, and less potent against VEGFR1/Flt-1, and approximately 10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β.

IC50 & Target: IC50: 4 nM (VEGFR2), 5.2 nM (VEGFR3)^[1]

In Vitro: Lenvatinib inhibits KIT kinase with an IC₅₀ value of 100 nM. lenvatinib inhibits SCF- and VEGF-induced tube formation in a dose-dependent manner with IC₅₀ values of 5.2 and 5.1 nM, respectively. Lenvatinib inhibits SCF-induced proliferation of another human SCLC, H526 cells, which expresses KIT, at the concentrations required for the inhibition of KIT kinase. The IC₅₀ values of Lenvatinib against phosphorylation of KDR and KIT in HUVEC are about 500 times lower than those against H146 proliferation in vitro^[1]. Lenvatinib inhibits both angiogenesis and lymphangiogenesis induced by human breast cancer cells, and significantly inhibits tumor growth of MDA-MB-231. Lenvatinib and bevacizumab treatment decreases MVD by almost the same extent^[2]. Lenvatinib inhibits proliferation at high concentrations (mean IC₅₀s 23.6-44.17 μM) in the majority of the cell lines, while the IC₅₀ in the KM12C colon cancer cell line is 9.54 μM^[3].

In Vivo: 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].