AZD1152
(Synonyms: 5-[[7-[3-[乙基[2-(磷酰氧基)乙基]氨基]丙氧基]-4-喹唑啉基]氨基]-N-(3-氟苯基)-1H-吡唑-3-乙酰胺,AZD-1152;AZD 1152) 目录号 : GC14709
AZD1152是一种高度选择性的Aurora B激酶（AURKB）抑制剂，IC50值为0.37nM。AZD1152是一种前体药物，在体内转化为活性形式AZD1152-hydroxyquinazoline pyrazol anilide（AZD1152-hQPA），主要用于研究与治疗急性髓系白血病等恶性肿瘤。
Cas No.:722543-31-9
Sample solution is provided at 25 µL, 10mM.
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AZD1152 is a highly selective Aurora B kinase (AURKB) inhibitor with an IC50 value of 0.37nM[1]. AZD1152 is a prodrug that is converted in vivo to its active form, AZD1152-hydroxyquinazoline pyrazol anilide (AZD1152-hQPA), and is primarily used for research and treatment of malignant tumors such as acute myeloid leukemia[2]. AZD1152 inhibits Aurora B kinase activity by competitively binding to its ATP binding site, affecting histone H3 phosphorylation, spindle assembly, and cytokinesis, thus inducing apoptosis and inhibiting tumor cell proliferation[3].
In vivo, AZD1152 (5, 25mg/kg) administered intraperitoneally to mice with MOLM13 cell xenograft tumors inhibited tumor growth. Furthermore, combination treatment with AZD1152 and vincristine or daunorubicin enhanced their anti-tumor effects[4]. AZD1152 (50, 100mg/kg) administered intraperitoneally to mice with H841 cell xenograft tumors for 10 days inhibited tumor growth and induced tumor regression[5]. AZD1152 (35mg/kg) administered intraperitoneally to mice with a colorectal cancer model for 4 days enhanced the cytotoxic effect of 8 Gy radiation on tumor cells[6].
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, The Journal of the American Society of Hematology, 2007, 110(6): 2034-2040.
[2] Aihara A, Tanaka S, Yasen M, et al. The selective Aurora B kinase inhibitor AZD1152 as a novel treatment for hepatocellular carcinoma[J]. Journal of hepatology, 2010, 52(1): 63-71.
[3] Borah N A, Reddy M M. Aurora kinase B inhibition: a potential therapeutic strategy for cancer[J]. Molecules, 2021, 26(7): 1981.
[4] Wilkinson R W, Odedra R, Heaton S P, et al. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis[J]. Clinical cancer research, 2007, 13(12): 3682-3688.
[5] Helfrich B A, Kim J, Gao D, et al. Barasertib (AZD1152), a small molecule Aurora B inhibitor, inhibits the growth of SCLC cell lines in vitro and in vivo[J]. Molecular cancer therapeutics, 2016, 15(10): 2314-2322.
[6] Tao Y, Leteur C, Calderaro J, et al. The aurora B kinase inhibitor AZD1152 sensitizes cancer cells to fractionated irradiation and induces mitotic catastrophe[J]. Cell Cycle, 2009, 8(19): 3172-3181.
AZD1152是一种高度选择性的Aurora B激酶（AURKB）抑制剂，IC50值为0.37nM[1]。AZD1152是一种前体药物，在体内转化为活性形式AZD1152-hydroxyquinazoline pyrazol anilide（AZD1152-hQPA），主要用于研究与治疗急性髓系白血病等恶性肿瘤[2]。AZD1152能够通过竞争性地结合Aurora B激酶的ATP结合位点抑制其活性，影响组蛋白H3磷酸化、纺锤体组装和胞质分裂，从而诱导肿瘤细胞凋亡并抑制其增殖[3]。
在体内，AZD1152（5, 25mg/kg）通过腹腔注射治疗MOLM13细胞异种移植小鼠，抑制了小鼠体内肿瘤的生长，AZD1152与长春新碱或柔红霉素联合使用还增强了它们的抗肿瘤能力[4]。AZD1152（50, 100mg/kg）通过腹腔注射治疗H841细胞异种移植小鼠10天，抑制了小鼠体内肿瘤的生长，引起了肿瘤消退[5]。AZD1152（35mg/kg）通过腹腔注射治疗结肠癌模型小鼠4天，增强了8Gy辐射对肿瘤细胞的杀伤作用[6]。
| Animal experiment [1]: | |
Animal models | Female immune-deficient BALB/c nude mice |
Preparation Method | Female immune-deficient BALB/c nude mice at 4 weeks of age were maintained in pathogen-free conditions with irradiated chow. Animals were bilaterally, subcutaneously injected with 2×106 MOLM13 cells/tumor in 0.1mL Matrigel. When MOLM13 cells formed palpable tumors, mice were divided randomly into control and treatment groups, and treatment was begun. AZD1152 (5 or 25mg/kg) with or without vincristine (0.2mg/kg) was given to mice by intraperitoneal injection 4 times a week or every another day, respectively. Daunorubicin (1mg/kg) was given to mice by intraperitoneal injection 6 times during 2 weeks of treatment either alone or in combination with AZD1152 (5mg/kg). Control diluent was given to the untreated control mice. Body weight and tumors were measured twice a week. At the end of the experiment, animals were killed and tumor weights were measured after their careful resection. Tumor tissue was collected for analysis. |
Dosage form | 5, 25mg/kg/day; i.p. |
Applications | AZD1152 inhibited the proliferation of MOLM13 xenografts in vivo. AZD1152 enhanced the ability of vincristine or daunorubicin to inhibit the proliferation of human MOLM13 leukemic xenografts in vivo. |
References: | |
| Cas No. | 722543-31-9 | SDF | |
| 别名 | 5-[[7-[3-[乙基[2-(磷酰氧基)乙基]氨基]丙氧基]-4-喹唑啉基]氨基]-N-(3-氟苯基)-1H-吡唑-3-乙酰胺,AZD-1152;AZD 1152 | ||
| 化学名 | 2-[ethyl-[3-[4-[[5-[2-(3-fluoroanilino)-2-oxoethyl]-1H-pyrazol-3-yl]amino]quinazolin-7-yl]oxypropyl]amino]ethyl dihydrogen phosphate | ||
| Canonical SMILES | CCN(CCCOC1=CC2=C(C=C1)C(=NC=N2)NC3=NNC(=C3)CC(=O)NC4=CC(=CC=C4)F)CCOP(=O)(O)O | ||
| 分子式 | C26H31FN7O6P | 分子量 | 587.54 |
| 溶解度 | ≥ 30 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.702 mL | 8.5101 mL | 17.0201 mL |
| 5 mM | 340.4 μL | 1.702 mL | 3.404 mL |
| 10 mM | 170.2 μL | 851 μL | 1.702 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet