Tozasertib

Tozasertib (VX-680, MK-0457) is a small-molecule Aurora kinase inhibitor. The Aurora kinases are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Tozasertib (VX-680) blocks cell-cycle progression and induces apoptosis in a diverse range of human tumor types. Tozasertib (VX-680) effectively inhibits proliferation of several different cell lines of clear cell renal carcinoma (IC50s < 10 μM) and blocks the growth of tumors in a rodent model of cancer (80 mg/kg), inhibiting H3 histone phosphorylation, to an increase of apoptotic cells, and to morphological changes such as vacuolization and swelling of the cells and nuclei. The combination of VX-680 and histone deacetylase inhibitor SAHA had a synergistic effect on the proliferation of HUH6 cells. Tozasertib (VX-680) might improve treatment results in HB with increased Aurora kinase activity by inhibiting cell proliferation and induction of apoptosis.