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AZD1152

现货
Catalog No.
A3214
Aurora B激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 950.00
现货
5mg
¥ 850.00
现货
10mg
¥ 1,450.00
现货
50mg
¥ 4,700.00
Ship with 10-15 days

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Background

AZD1152 is a highly selective inhibitor of Aurora kinases with IC50 values of 1.37 μM and 0.37 nM for Aurora A and Aurora B, respectively [1].
AZD1152 is a dihydrogen phosphate pro-drug of HQPA which is a highly potent and specific inhibitor of the serine/threonine kinase Aurora kinases. The expression of Aurora kinase A and B are found to be related with the development of various cancers such as ovarian, pancreatic, breast and colon. Since that, the Aurora family is regarded as attractive target for anticancer treatment. As a selective Aurora kinase inhibitor, AZD1152 showed no significant effect on other kinases including JAK2, FLT3 and Abl. Besides that, AZD1152 exerted potent antitumor activities through inhibiting tumor cell proliferation and inducing apoptosis [1].
AZD1152 treatment potently inhibited cell growth in various leukemic cells including ALL PALL-2, MV4-11 and MOLM13 with IC50 values of 5, 1and 2.8 nM, respectively. AZD1152 also inhibited clone formation of freshly isolated leukemia cells with IC50 values of less than 3 nM. For the colon cancer HCT-116 cells, incubation of AZD1152 at dose of 30 nM for one day resulted in 80% cell number reduction after 4 days drug wash out. In prostate cancer DU145 and PC3 cells, AZD1152 caused decrease of G0/G1-phase cells and induced G2/M cell cycle arrest. Moreover, AZD1152 treatment enhanced the radio sensitivity of prostate cancer cells which were androgen-insensitive [1, 2 and 3].
In mice model with human MOLM13 cell xenografts, administration of AZD1152 at dose of 25 mg/kg significantly inhibited tumor growth. The combination treatment of AZD1152 at dose of 5 mg/kg and vincristine at dose of 0.2 mg/kg resulted in almost 100% inhibition of tumor growth of MOLM13 xenografts. In mice injected with MiaPaCa-2cells, the combination of AZD1152 and gemcitabine showed more than double effective than the single treatment [1 and 2].
References:
[1] Yang J, Ikezoe T, Nishioka C, Tasaka T, Taniguchi A, Kuwayama Y, Komatsu N, Bandobashi K, Togitani K, Koeffler HP, Taguchi H, Yokoyama A. 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.  
[2] Azzariti A, Bocci G, Porcelli L, Fioravanti A, Sini P, Simone GM, Quatrale AE, Chiarappa P, Mangia A, Sebastian S, Del Bufalo D, Del Tacca M, Paradiso A. Aurora B kinase inhibitor AZD1152: determinants of action and ability to enhance chemotherapeutics effectiveness in pancreatic and colon cancer. Br J Cancer. 2011 Mar 1;104(5):769-80.
[3] Niermann KJ, Moretti L, Giacalone NJ, Sun Y, Schleicher SM, Kopsombut P, Mitchell LR, Kim KW, Lu B. Enhanced radiosensitivity of androgen-resistant prostate cancer: AZD1152-mediated Aurora kinase B inhibition. Radiat Res. 2011 Apr;175(4):444-51.

文献引用

1. Oser MG, Fonseca R, et al. "Cells Lacking the RB1 Tumor Suppressor Gene are Hyperdependent on Aurora B Kinase for Survival." Cancer Discov. 2018 Oct 29. pii: CD-18-0389. PMID:30373918

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt587.54
Cas No.722543-31-9
FormulaC26H31FN7O6P
SynonymsAZD-1152;AZD 1152
Solubility≥5.88 mg/mL in DMSO, <2.46 mg/mL in EtOH, <2.25 mg/mL in H2O
Chemical Name2-[ethyl-[3-[4-[[5-[2-(3-fluoroanilino)-2-oxoethyl]-1H-pyrazol-3-yl]amino]quinazolin-7-yl]oxypropyl]amino]ethyl dihydrogen phosphate
SDFDownload SDF
Canonical SMILESCCN(CCCOC1=CC2=C(C=C1)C(=NC=N2)NC3=NNC(=C3)CC(=O)NC4=CC(=CC=C4)F)CCOP(=O)(O)O
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

来自患者的白血病细胞,来自健康志愿者的骨髓单核细胞

溶解方法

该化合物在DMSO中的溶解度大于5.9 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

1-100 nM

应用

AZD1152-HQPA(1-100 nM)诱导多种类型的白血病细胞的生长停滞,针对费城染色体阳性ALL PALL-2、急性单核细胞白血病MOLM13和双表型白血病MV4-11细胞的IC50约为5、12和8nM。AZD1152(3 μM,3小时)显著降低新鲜分离的白血病细胞中磷酸化组蛋白H3的表达。在MOLM13和PALL2细胞中,AZD1152以剂量和时间依赖的方式增加细胞4N/8N DNA含量。AZD1152-HQPA治疗(1-10 nM)24或48小时以剂量依赖性方式诱导细胞凋亡。

动物实验[1]:

动物模型

用人MOLM13细胞异种移植的雌性免疫缺陷型BALB/c裸鼠

给药剂量

5或25 mg/kg,腹腔注射,每周四次或隔天给药

应用

AZD1152 (25 mg/kg)显著抑制AZD1152治疗肿瘤的生长和重量。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1] Yang J, Ikezoe T, Nishioka C, 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[J]. Blood, 2007, 110(6): 2034-2040.

[2] Lee TX1, Packer MD, Huang J, Akhmametyeva EM, Kulp SK, Chen CS, Giovannini M, Jacob A, Welling DB, Chang LS. Growth inhibitory and anti-tumour activities of OSU-03012, a novel PDK-1 inhibitor, on vestibular schwannoma and malignant schwannoma cells. Eur J Cancer. 2009 Jun;45(9):1709-20.

质量控制

质量控制和MSDS

批次:

化学结构

AZD1152

相关生物数据

AZD1152