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Barasertib (AZD1152-HQPA)

现货
Catalog No.
A4112
Aurora Kinase B抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 830.00
现货
5mg
¥ 790.00
现货
10mg
¥ 1,040.00
现货
50mg
¥ 3,710.00
现货

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Background

Barasertib, previously known as AZD1152-hydroxyquinazoline pyrazol anilide (HQPA), is a potent aurora kinase inhibitor, which is resulted from rapid phosphatase-mediated cleavage of the precursor, AZD1152, in serum following parenteral administration in vivo. It shows inhibitory effects against a broad range of aurora kinases, including aurora A kinase (AKB), aurora B kinase (ABK), and aurora C kinase (ACK) with inhibition constant (Ki) of 1369 nM, 0.36 nM, and 17.0 nM respectively, as well as the FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation. Barasertib has demonstrated anti-tumor activity against a range tumor cell lines including those of leukaemic acute myeloid leukemia (AML) origin.

Reference

Martin Grundy, Claire Seedhouse, Nigel H Russell and Monica Pallis. P-glycoprotein and breast cancer resistance protein in acyte myeloid leukaemia cells treated with the aurora-B kinase inhibitor barasertib-Hqpa. BMC Cancer 2011, 11:254

Mike Dennis, Michelle Davies, Stuart Oliver, Roy D’Souza, Laura Pike, and Paul Stockman. Phase I study of the aurora B kinase inhibitor barasertib (AZD1152) to assess the pharmacokinetics, metabolism and excretion in patients with acute myeloid leukemia. Cancer Chemother Pharmacol (2012) 70:461-469

文献引用

1.Christine M Field, James F Pelletier, et al. "Disassembly of actin and keratin networks by Aurora B kinase at the midplane of cleaving Xenopus laevis eggs." bioRxiv. 2019 January 06.
2.Shodai Tanaka, Kaori Senda-Murata, et al. "Live cell imaging of anaphase bridge formation and the subsequent cleavage furrow regression induced by the Aurora B kinase inhibitor AZD1152-HQPA." Bioimages.2017.10.05.
3.Hanley ML, Yoo TY, et al. "Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin." Mol Biol Cell. 2017 Apr 12. pii: mbc.E16-12-0860. PMID:28404751

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt507.56
Cas No.722544-51-6
FormulaC26H30FN7O3
SynonymsAZD1152-HQPA,AZD-1152HQPA, AZD1152 HPQA,INH 34
Solubility≥25.4 mg/mL in DMSO, <2.27 mg/mL in EtOH, <2.28 mg/mL in H2O
Chemical Name2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide
SDFDownload SDF
Canonical SMILESCCN(CCCOC1=CC2=C(C=C1)C(=NC=N2)NC3=NNC(=C3)CC(=O)NC4=CC(=CC=C4)F)CCO
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

HL-60细胞

制备方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

25 nM,72 hours

实验结果

在Barasertib处理的24-48小时内,细胞4N和8N的DNA含量增加,意味着产生了多倍体。48-72小时后,与未处理的细胞相比,barasertib-HQPA通过增加亚G1群体数量,诱导凋亡性细胞死亡。 在24-48小时明显诱导多倍体产生,此后,细胞核显示出典型的凋亡形态,例如核碎裂和固缩。这些观察结果符合流式细胞术分析的结果。

动物实验[2]:

动物模型

注射SW620、Colo205或HCT116细胞的雌性裸鼠

给药剂量

皮下注射,150 mg/kg/day,48小时微量泵输注

实验结果

在SW620、HCT116和Colo205异种移植肿瘤中分别观察到79%(P < 0.001,第23天)、60%(P < 0.001,第25天)和81%(P < 0.05,第21天)的肿瘤生长抑制。Colo205异种移植物对barasertib治疗最敏感,在细胞移植后21天平均肿瘤体积(±SEM)为0.42 ± 0.19 cm3,而对照动物为2.24 ± 0.75 cm3(P < 0.05)。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Yamauchi T, Uzui K, Shigemi H, et al. Aurora B inhibitor barasertib and cytarabine exert a greater-than-additive cytotoxicity in acute myeloid leukemia cells. Cancer science, 2013, 104(7): 926-933.

[2] Alferez D G, Goodlad R A, Odedra R, et al. Inhibition of Aurora-B kinase activity confers antitumor efficacy in preclinical mouse models of early and advanced gastrointestinal neoplasia. International journal of oncology, 2012, 41(4): 1475-1485.

生物活性

描述 Barasertib (AZD1152-HQPA)是一种高选择性的Aurora B抑制剂,IC50值为0.37 nM,比对Aurora A的选择性高约100倍。
靶点 Aurora B          
IC50 0.37 nM          

质量控制

化学结构

Barasertib (AZD1152-HQPA)

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Barasertib (AZD1152-HQPA)

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Barasertib (AZD1152-HQPA)