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Tozasertib (VX 680; MK-0457) is an inhibitor of Aurora A/B/C kinases with Kis of 0.6, 18, 4.6 nM, respectively.

Tozasertib induces similar cytotoxicity with IC50 of approximately 300 nM and exhibits an AUR B-like inhibitory phenotype of G2/M arrest, endoreduplication and apoptosis in BaF3 cells transfected with ABL or FLT-3 (mutant and wild type) kinases. Tozasertib prevents the CAL-62 proliferation in a time-dependent manner. Tozasertib treatment for 14 days significantly decreases the number and size of colonies by approximately 70% in the 8305C and 90% in the CAL-62, 8505C and BHT-101. Treatment of the different ATC cells with Tozasertib inhibits proliferation with the IC50 between 25 and 150 nM. The Tozasertib significantly impairs the ability of the different cell lines to form colonies in soft agar. Analysis of caspase-3 activity indicates that Tozasertib induces apoptosis in the different cell lines. CAL-62 cells exposed for 12 hours to Tozasertib show an accumulation of cells with ≥ 4N DNA content. Time-lapse analysis demonstrates that Tozasertib-treated CAL-62 cells exit metaphase without dividing. Moreover, histone H3 phosphorylation is abrogated following Tozasertib treatment[2]. Tozasertib has significant inhibitory activity against BCR-Abl bearing the T315I mutation in patient-derived samples[3].

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