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首页 >> Signaling Pathways >> Chromatin/Epigenetics >> Aurora Kinase >> Barasertib (AZD1152-HQPA)
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Barasertib (AZD1152-HQPA)Aurora Kinase B抑制剂

Barasertib (AZD1152-HQPA)

产品编号:A4112
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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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Sample solution is provided at 25 µL, 10mM.

引用文献

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

质量控制

化学结构

Barasertib (AZD1152-HQPA)

相关生物数据

Barasertib (AZD1152-HQPA)

相关生物数据

Barasertib (AZD1152-HQPA)

相关生物数据

Barasertib (AZD1152-HQPA)

相关生物数据

Barasertib (AZD1152-HQPA)

相关生物数据

Barasertib (AZD1152-HQPA)

Barasertib (AZD1152-HQPA) Dilution Calculator

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Barasertib (AZD1152-HQPA) Molarity Calculator

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化学性质

CAS号 722544-51-6 SDF Download SDF
别名 AZD1152-HQPA,AZD-1152HQPA, AZD1152 HPQA,INH 34
化学名 2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide
SMILES CCN(CCCOC1=CC2=C(C=C1)C(=NC=N2)NC3=NNC(=C3)CC(=O)NC4=CC(=CC=C4)F)CCO
分子式 C26H30FN7O3 分子量 507.56
溶解度 ≥25.4 mg/mL in DMSO, <2.27 mg/mL in EtOH, <2.28 mg/mL in H2O 储存条件 Store at -20°C
物理性状 A solid 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。

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          

实验操作

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.

研究更新

3. Aurora B inhibitor barasertib and cytarabine exert a greater-than-additive cytotoxicity in acute myeloid leukemia cells. Cancer Sci. 2013 Jul;104(7):926-33. doi: 10.1111/cas.12164. Epub 2013 May 12.
Abstract
As an active metabolite of Barasertib, barasertib-HQPA is an inhibitor of aurora B that potently inhibited growth of HL cells by inducing polyploidy and apoptosis. In order to provide a greater-than-additive cyctotoxicity to HL cells, barasertib-HQPA must be applied before or concurrently with ara-C.
4. Effect of the drug transporters ABCG2, Abcg2, ABCB1 and ABCC2 on the disposition, brain accumulation and myelotoxicity of the aurora kinase B inhibitor barasertib and its more active form barasertib-hydroxy-QPA. Invest New Drugs. 2013 Oct;31(5):1125-35. doi: 10.1007/s10637-013-9923-1. Epub 2013 Jan 13.
Abstract
Both barasertib and barasertib-hQPA could be efficiently transported by BCRP and MDR1, in which significant barasertib resistance has been observed. MRP2 neither transported barasertibe nor affected its cytotoxicity.
5. Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. Invest New Drugs. 2013 Apr;31(2):370-80. doi: 10.1007/s10637-012-9825-7. Epub 2012 Jun 2.
Abstract
Barasertib, an Aurora B Kinase inhibitor, was generally well tolerated in patients with advanced solid malignancies with MTDs of 150 mg and 220 mg for 48-h continuous infusion and two 2-h infusion respectively, which caused neutropenia as the DLT and mild to modest adverse side effects of hematologic or gastrointestinal etiology.

产品描述

Barasertib(AZD1152-羟基喹唑啉吡唑酰基苯胺(HQPA))是一种有效的Aurora激酶抑制剂。在体内,通过胃肠外给药后,血清中的前体AZD1152被磷酸酶快速裂解,从而产生AZD1152-HQPA。Barasertib对广泛的aurora激酶均有抑制效应,包括aurora A激酶(AKB)、aurora B激酶(ABK)和aurora C激酶(ACK),Ki值分别为1369 nM、0.36 nM和17.0 nM。Barasertib也抑制FMS样酪氨酸激酶3内部串联重复(FLT3-ITD)突变。Barasertib对一系列肿瘤细胞系均具有抗肿瘤活性,包括白血病急性髓细胞白血病(AML)来源的肿瘤细胞。

参考文献:
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