Abstract: Objective To screen 8 series of LY compounds, which are c-Met tyrosine kinase inhibitors, and evaluate their anti-tumor effect in vitro and in vivo. Methods Preliminary screening was carried out by detecting the c-Met kinase phosphorylation inhibition activity of the compounds. CCK8 assay was adopted for secondary anti-tumor screen of the selected compounds using MKN-45, U87MG, Caki-1, PC-3 cell lines in vitro. The sc transplanted tumor model of U87MG cells in nude mice was established to evaluate the antitumor activity in vivo. Results Four compounds (LY22, LY25, LY28, LY32) with better activities were selected by HTRF method, where LY28 had better inhibitory effect on c-Met than Crizotinib. The above active compounds showed different degrees of inhibition on four kinds of target cells (MKN-45, U87MG, Caki-1 and PC-3) by CCK8 method, and the inhibition of LY28 was the most obvious. Antitumor activity in vivo showed that LY28 could significantly inhibited tumors growth in a dose-dependent manner. The tumors inhibition rate in high-dose of LY28 was 78.13%, close to 80.47% in Crizotinib group. Conclusion The compound LY28 has good antitumor activity in vitro and in vivo, which will be a new tyrosine kinase inhibitor.

Key words: c-Met, antitumor, activity screening, tyrosine kinase inhibitor