The Aurora family of serine/threonine kinases, which consists of Aurora A, B and C, plays an important role in chromosome alignment, segregation, and cytokinesis during mitosis. AZD1152-HQPA, the active drug form converted from AZD1152 (Barasertib) in human plasma, is a specific Aurora B inhibitor with Ki value of 0.36nM versus 1369nM for A kinase. Consistent with Aurora B kinase inhibition, treatment with AZD1152-HQPA caused a dose-dependent inhibition of histone H3 phosphorylation on Ser10 site, with IC50 of 10.27nM, in SW620 colorectal tumor cells and led to increased polyploidy following a 48-h exposure. This activity of AZD1152-HQPA can also observed in an in vivo study. Administration of AZD1152 at dose ranging in 10-150mg/kg/d via an osmotic mini-pump for 48h inhibited growth in a panel of human tumor xenografts, including SW620, Colo205, A549 and HL-6, suggesting that AZD1152 was active against a variety of solid tumors including colon, breast and lung cancers[1]. AZD1152 also had effect in hematologic malignancies. In the presence of AZD1152-HQPA, the clonogenic growth of freshly isolated leukemia cells tested was effectively inhibited with IC50 values ranging in 1-3nM. Exposure of MOLM13 cells to AZD1152-HQPA (1-10nM) for 24 or 48 hours induced apoptosis in a dose-dependent manner. AZD1152-HQPA alone or combined with vincristine or daunorubicin significantly inhibited the proliferation of MOLM13 cells in murine xenograft model[2].
作用机制
AZD1152-HQPA can bind to the ATP-binding pocket of Aurora B.[2]
Barasertib-HQPA 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
BALM-14
12.5/25/50 nM
Apoptosis Assay
48 h
increases the levels of the cleaved forms of PARP and caspase 3
19823168
BALM-27
12.5/25/50 nM
Apoptosis Assay
48 h
increases the levels of the cleaved forms of PARP and caspase 3
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