Tozasertib

639089-54-6

C23H28N8OS

DMSO : >= 106.67 mg/mL (229.60 mM)

Cell Cycle/DNA Damage; Epigenetics; Autophagy

Tozasertib (VX 680; MK-0457) is an inhibitor of Aurora A/B/C kinases with K_is of 0.6, 18, 4.6 nM, respectively. IC50 & Target: Ki: 0.6 nM (Aurora A), 18 nM (Aurora B), 4.6 nM (Aurora C)^[1] In Vitro: 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].