AZD1152

AZD1152的生物活性 AZD1152 (barasertib),  pro-drug of barasertib-hQPA(HY-10126), is a selective Aurora B kinase inhibitor, AZD1152 inhibited the proliferation various types of human leukemia cells with an IC50 ranging from 3 nM to 40 nM. IC50 value: 3-40 nM (HL-60, NB4, MOLM13; PALL-2; MV4-11; EOL-1; K562 cell) [1] Target: Aurora B kinase in vitro: AZD1152, a highly selective inhibitor of Aurora B kinase, on various types of human leukemia cells. AZD1152 inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 nM to 40 nM, as measured by thymidine uptake on day 2 of culture [1]. The selective Aurora B inhibitor AZD1152-induced apoptotic death in myeloma cell lines at nanomolar concentrations, with a cell cycle phenotype consistent with that reported previously for Aurora B inhibition [3]. AZD1152 exerted antiproliferative or cytotoxic effects in all cell lines studied, inhibited the phosphorylation of histone H3 (pHis H3) on Ser10 in a dose-dependent manner, and resulted in cells with >4N DNA content. THP-1 cells treated with AZD1152 accumulated in a state of polyploidy and showed a senescent response to the drug, in contrast to the apoptotic response seen in other cell lines [4]. in vivo: AZD1152 potentiated the action of vincristine and daunorubicin in a MOLM13 murine xenograft model [1]. AZD1152 potently inhibited the growth of human colon, lung, and hematologic tumor xenografts (mean tumor growth inhibition range, 55% to > or =100%; P < 0.05) in immunodeficient mice [2]. AZD1152 profoundly affected the growth of AML cell lines and primary AML in an in vivo xenotransplantation model [4]. Clinical: Phase 2