c-Met/RON Dual Kinase Inhibitor is a potent inhibitor against the kinase activities of HGF receptor c-Met and MSP (Macrophage Stimulating Protein) receptor RON with IC50 of 4 and 9 nM, respectively, and it is reported to inhibit NIH3T3 TRP-Met and U-87 tumor growth in mice in vivo in a dose-dependent manner.
Recepteur d'origine nantais (RON) and c-Met are receptor tyrosine kinases involved in cell proliferation, migration, and invasion, all of which are key biological events in tumorigenesis. RON-IN-1 is a potent inhibitor of both RON and c-Met that selectively inhibited their kinase activities with IC50 values of 9nM and 4nM, respectively. It shows weak inhibitory activity towards Lck, Tie2, Src, and BTK with IC50 values ranging from 160 to 710nM. In HT-29 and BxPC3 cells, RON-IN-1 at 10 – 1000nM inhibited hepatocyte growth factor-mediated c-Met phosphorylation and downstream signaling in a dose-dependent manner. RON-IN-1 at 10 – 1000nM also inhibited NIH3T3 TPR-Met cell migration. In NIH3T3 RON and BxPC3 cells, treatment with RON-IN-1 (10 – 1000nM) dose-dependently inhibited RON signaling and functional activity. Treatment of NIH3T3 TPR-Met tumor-bearing mice with RON-IN-1 (30 or 100mg/kg once daily, or 30mg/kg twice daily) significantly inhibited tumor growth compared with vehicle-treated control animals. RON-IN-1 (30 or 100mg/kg once daily) also significantly and dose-dependently reduced tumor growth in mice bearing established HT-29 tumors[1].
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