In Vitro: Barasertib-HQPA (3 μM, 3 hours) significantly decreases expression of the phosphorylated forms of histone H3 in freshly isolated leukemia cells. ?Barasertib-hydroxyquinazoline pyrazol anilide (HQPA) is converted rapidly to the active Barasertib-HQPA in plasma. ?Barasertib-HQPA treatment induced defective cell survival, polyploidy, and cell death in LNCaP cell line. ?Barasertib-HQPA induces a marked anti-propliferative effect accompanied by the appearance of a polyploid population, which in most cases led to apoptosis.
In Vivo: Barasertib-HQPA (AZD1152, 25 mg/kg) markedly suppresses the growth and weights of AZD1152-treated tumors. ?Barasertib-HQPA (AZD1152, 5 mg/kg) enhances the ability of vincristine or daunorubicin to inhibit the proliferation of human MOLM13 leukemic xenografts. ?Barasertib-HQPA (AZD1152, (10-150 mg/kg/d) potently inhibited the growth of human colon, lung, and hematologic tumor xenografts (mean tumor growth inhibition range, 55% to z100%; P < 0.05) in immunodeficient mice.