货号：L5974

储存条件：粉末-20°C可保存3年；液体-80°C可保存12月。

产品描述

SCF is abundantly expressed in a broad spectrum of human malignancies, such asSCLC, NSCLC, colon, breast and renal cancers, acting through both activation of its receptor KIT and paracrine angiogenesis factor. Lenvatinib is a multiple receptor tyrosine kinases inhibitor with IC50 values of 4.0nM, 5.2nM, 22nM, 39nM, 46nM, 51nM and 100nM for VEGFR2, VEGFR3, VEGFR1, PDGFRβ, FGFR1, PDGFRα and Kit (measured by HTRF assays), respectively. Exposure to Lenvatinib inhibited SCF-induced KIT (Tyr719) phosphorylation and VEGF-induced KDR (Tyr996) phosphorylation in HUVEC with IC50 values of 1.9nM and 0.83nM. Consistent with its inhibition of this two targets, the sandwich tube formation (sTF) assay showed that treatment with Lenvatinib inhibited either VEGF or SCF-induced tube formation of HUVEC in a dose-dependent manner with IC50s of 5.2 and 5.1nM, respectively. Though Lenvatinib did not show the potent inhibitory activities against H146 cells expressing SCF, but not KIT, it inhibited SCF-induced cell proliferation of human SCLC, H526 cells expressing KIT, suggesting the inhibition by Lenvatinib on cell growth through paracrine. Oral administration of Lenvatinib at dose of 30 and 100 mg/kg (BID, QDx21) caused tumor growth in a dose-dependent manner in H146 xenograft, while tumor regression achieved at dose of 100mg/kg with decreased microvessel density.

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