Pharmacodynamic screening of anticancer agents used as c-Met inhibitor in vitro and in vivo / 天津医药

ABSTRACT

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