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Barasertib-HQPA

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Chemical Structure| 722544-51-6 同义名 : AZD1152-HQPA;AZD2811;Defosbarasertib;Barasertib;INH-34
CAS号 : 722544-51-6
货号 : A153304
分子式 : C26H30FN7O3
纯度 : 99%+
分子量 : 507.56
MDL号 : MFCD17392583
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(39.4 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+35% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 50 mg/mL suspension

生物活性
靶点

  • Aurora B

    Aurora B, IC50:0.37 nM
描述 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]
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 19823168
BJAJ 500 nM Growth Inhibition Assay 0-72 h inhibits cell growth significantly 21371446
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.97mL

0.39mL

0.20mL

9.85mL

1.97mL

0.99mL

19.70mL

3.94mL

1.97mL
参考文献

[1]Wilkinson RW, Odedra R, et al. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res. 2007 Jun 15;13(12):3682-8.

[2]Yang J, Ikezoe T, et al. AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood. 2007 Sep 15;110(6):2034-40. Epub 2007 May 10.

[3]Sessa F, Villa F, et al. Structure of Aurora B-INCENP in complex with barasertib reveals a potential transinhibitory mechanism. Acta Crystallogr F Struct Biol Commun. 2014 Mar;70(Pt 3):294-8.

[4]Helfrich BA, Kim J, et al. Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo. Mol Cancer Ther. 2016;15(10):2314-2322.