Aurora B (IC50 = 10.37 nM)
Barasertib-HQPA (3 μM, 3 hours) considerably reduces the expression of histone H3 phosphorylation in newly isolated leukemia cells[1].
Barasertib-hydroxyquinazoline pyrazol anilide (HQPA)] is quickly changed in plasma to the active form of barasertib-HQPA[2].
Barasertib-HQPA is employed in the in vitro research[3].
Barasertib-HQPA causes a polyploid population to emerge along with a noticeable anti-propliferative effect that, in most cases, results in apoptosis[4].

体外活性：AZD1152 对 Aurora B 的选择性是 Aurora A 的 3000 倍以上，Aurora A 的 IC50 为 1.368 μM。 AZD1152 对 50 种其他丝氨酸-苏氨酸和酪氨酸激酶（包括 FLT3、JAK2 和 Abl）的活性甚至更低。 AZD1152 抑制造血恶性细胞的增殖，如 HL-60、NB4、MOLM13、PALL-1、PALL-2、MV4-11、EOL-1、THP-1 和 K562 细胞，IC50 为 3-40 nM，显示比另一种极光激酶抑制剂 ZM334739 效力约 100 倍，其 IC50 为 3-30 μM。 AZD1152 抑制 MOLM13 和 MV4-11 细胞的克隆生长，IC50 分别为 1 nM 和 2.8 nM，以及新鲜分离的伊马替尼耐药白血病细胞，IC50 值为 1-3 nM，与骨髓单核细胞相比更显着。 IC50 值 >10 nM 的细胞。 AZD1152 诱导细胞积累 4N/8N DNA 含量，随后以剂量和时间依赖性方式发生细胞凋亡。激酶测定：AZD1152 对 Aurora B 的选择性是 Aurora A 的 3000 倍以上，Aurora A 的 IC50 为 1.368 μM。 AZD1152 对 50 种其他丝氨酸-苏氨酸和酪氨酸激酶（包括 FLT3、JAK2 和 Abl）的活性甚至更低。细胞测定：将细胞暴露于不同浓度的AZD1152 24或48小时。通过 3 H-胸苷摄取（收获前 6 小时添加同位素）来测量细胞增殖，并根据剂量反应曲线计算诱导 50% 生长抑制 (IC50) 的浓度。通过流式细胞术进行细胞周期分析。采用annexin V-FITC凋亡检测试剂盒检测细胞凋亡。

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活性代谢物 AZD1152-HQPA 处理48小时后，通过[³H]-胸腺嘧啶核苷摄入法测定，可抑制一系列人类白血病细胞系（包括HL-60、NB4、MOLM13、PALL-2、MV4-11、EOL-1、K562）的增殖，IC50值范围为3 nM至40 nM。[1]
AZD1152-HQPA 抑制MOLM13和MV4-11细胞系的克隆形成生长，IC50值分别为1 nM和2.8 nM。[1]
在来自患者的原代白血病细胞（n=10）中，AZD1152-HQPA 在所有病例中均能抑制集落形成，IC50均小于3 nM。相比之下，对健康志愿者骨髓单个核细胞的IC50 >10 nM。[1]
AZD1152-HQPA (10 nM，24小时) 显著降低了MOLM13和MV4-11细胞中表达磷酸化组蛋白H3 (Ser10)（Aurora B激酶的底物）的细胞比例，证实了靶点抑制。在原代患者细胞中也观察到了类似效果。[1]
用 AZD1152-HQPA (1-10 nM) 处理MOLM13和PALL-2细胞，可诱导细胞发生剂量和时间依赖性的4N/8N DNA含量（多倍体）积累，表明细胞退出有丝分裂但未发生胞质分裂。[1]
通过膜联蛋白V/PI染色法测定，AZD1152-HQPA (1-10 nM) 以剂量依赖性的方式诱导MOLM13细胞凋亡。例如，3 nM和10 nM在48小时分别诱导了6%和50%的细胞凋亡。[1]
AZD1152-HQPA 与长春新碱（微管蛋白解聚剂）或柔红霉素（拓扑异构酶II抑制剂）联用，对PALL-2和MOLM13细胞具有协同抗增殖作用，联合指数（CI）值 < 1。[1]
蛋白质印迹分析显示，AZD1152-HQPA 增强了长春新碱或柔红霉素在PALL-2和MOLM13细胞中诱导的PARP切割（细胞凋亡标志物）。[1]

单独施用 AZD1152 (25 mg/kg) 可显着抑制 MOLM13 异种移植物的生长，这一点通过观察坏死组织和吞噬细胞的浸润得到证实。此外，AZD1152（10-150 mg/kg/天）以剂量依赖性方式显着抑制多种人类实体瘤异种移植物的生长，包括结肠癌、乳腺癌和肺癌。

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在皮下植入MOLM13白血病细胞的免疫缺陷小鼠异种移植模型中，腹腔注射 AZD1152 (25 mg/kg，每周4次，持续2周) 与对照组相比，显著抑制了肿瘤生长并降低了最终肿瘤重量（平均肿瘤体积：71 vs 1261 mm³；平均肿瘤重量：78 vs 583 mg）。在此剂量下，未观察到消瘦或其他明显毒性迹象。治疗小鼠的肿瘤组织学检查显示坏死组织伴有吞噬细胞浸润，未检测到白血病细胞。[1]
AZD1152 (5 mg/kg) 增强了长春新碱 (0.2 mg/kg) 在MOLM13异种移植模型中的抗肿瘤活性。联合用药几乎完全抑制了肿瘤生长，与任一单药相比，肿瘤重量显著降低，且未引起体重减轻。[1]
AZD1152 (5 mg/kg) 也增强了柔红霉素 (1 mg/kg) 在同一模型中的作用，导致更强的肿瘤生长抑制。然而，该方案下的柔红霉素单药治疗对小鼠具有毒性，表现为体重减轻。[1]

体外研究。[2]
通过高含量图像分析筛选确定磷酸化组蛋白H3（PhH3）抑制。接种在96孔板中的SW620细胞与AZD1152-HQPA一起孵育24小时，然后在3.7%甲醛中固定30分钟。然后用PBS洗涤细胞，用0.5%Triton X-100渗透，并在室温下用兔抗PhH3（Ser10）抗体（1:100）染色1小时。用PBS洗涤后，将细胞与Alexa Fluor 488山羊抗兔抗体（1:200）和赫斯特染色（1:10000）在室温下孵育1小时。使用靶激活算法在阵列扫描II上分析PhH3的细胞水平，以计算PhH3阳性细胞的百分比。在Origin（7.5版）中计算单个IC50值，并使用几何平均值（即转换回基数10的对数值的平均值）对数据进行总结。

细胞增殖测定[1]。
细胞类型： AML 系（HL-60、NB4、MOLM13）、ALL 系（PALL-2）、双表型白血病（MV4-11）、急性嗜酸性粒细胞白血病（EOL-1）、以及慢性粒细胞白血病K562细胞的急变。
测试浓度：0-100 nM。 (Barasertib -HQPA)
孵育时间： 48 小时。
实验结果：IC50值范围为3 nM至40 nM。

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集落形成试验[1]
如前所述，通过使用甲基纤维素培养基H4534的集落形成试验评估AZD1152对白血病细胞以及正常骨髓单核细胞的集落生长的影响。

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流式细胞术细胞周期分析[1]
在12孔板中，以5×105个细胞/mL的浓度用AZD1152-HQPA（1-10nM）孵育2天的白血病细胞进行细胞周期分析。

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细胞凋亡检测[1]
根据制造商的说明，通过膜联蛋白V-FITC凋亡检测试剂盒测量AZD1152-HQPA诱导白血病细胞凋亡的能力。

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增殖实验（[³H]-胸腺嘧啶核苷摄入法）： 将白血病细胞与不同浓度的 AZD1152-HQPA (1-100 nM) 在液体培养基中培养48小时。在培养结束前6小时加入[³H]-胸腺嘧啶核苷。然后收集细胞，测量掺入的放射性以评估DNA合成和细胞增殖。根据剂量反应曲线计算导致50%生长抑制的浓度（IC50）。[1]
克隆形成实验： 将白血病细胞（细胞系为1x10⁵ cells/mL，原代样本使用原代患者细胞）与含有细胞因子的甲基纤维素半固体培养基混合。将 AZD1152-HQPA (0.3-10 nM) 或溶媒对照加入孔中。铺板后，在37°C、5% CO₂的湿润环境中孵育10-14天。然后在显微镜下计数集落（>50个细胞的细胞团）。确定克隆形成生长的IC50。[1]
磷酸化组蛋白H3 (Ser10) 流式细胞术： 用 AZD1152-HQPA（例如，3-10 nM）处理细胞指定时间（例如，3或24小时）。然后固定、透化细胞，并用针对磷酸化组蛋白H3 (Ser10) 的特异性荧光标记抗体染色。使用流式细胞术定量阳性细胞的百分比。[1]
流式细胞术细胞周期分析： 用 AZD1152-HQPA (1-10 nM) 处理细胞24或48小时。收集细胞，固定，用DNA结合染料（如碘化丙啶）染色，并用流式细胞仪分析。确定细胞在不同周期（G0/G1、S、G2/M）及具有多倍体DNA含量（4N, 8N）的分布。[1]
细胞凋亡实验（膜联蛋白V/碘化丙啶染色）： 用 AZD1152-HQPA (1-10 nM) 处理细胞24或48小时。收集贴壁和悬浮细胞，用FITC标记的膜联蛋白V和碘化丙啶（PI）染色，并用流式细胞仪分析。区分早期凋亡细胞（膜联蛋白V+/PI-）、晚期凋亡/坏死细胞（膜联蛋白V+/PI+）和活细胞（膜联蛋白V-/PI-）。[1]
蛋白质印迹分析： 用 AZD1152-HQPA 和/或化疗药物（长春新碱、柔红霉素）处理细胞指定时间（例如，12小时）。裂解细胞，定量蛋白质，通过SDS-PAGE分离并转印至膜上。用针对目标蛋白（如切割的PARP，用于检测凋亡）和α-微管蛋白（上样对照）的一抗孵育膜，然后使用相应的二抗并通过化学发光法检测。[1]
联合指数分析： 将PALL-2或MOLM13细胞与不同浓度的 AZD1152-HQPA (0.3-10 nM) 和长春新碱 (0.1-1 µM) 或柔红霉素 (3-30 nM) 共培养48小时。通过[³H]-胸腺嘧啶核苷摄入法评估增殖情况。使用中效原理（Chou-Talalay法）分析剂量反应数据，计算不同效应水平（如IC50、IC75、IC90）下的联合指数（CI）。CI < 1表示协同作用。[1]

Mice[1]
Female immune-deficient BALB/c nude mice at 4 weeks of age were were maintained in pathogen-free conditions with irradiated chow. Animals were bilaterally, subcutaneously injected with 2 × 106 MOLM13 cells/tumor in 0.1 mL Matrigel or every another day, respectively. Daunorubicin (1 mg/kg) was given to mice by intraperitoneal injection 6 times during 2 weeks of treatment either alone or in combination with AZD1152 (5 mg/kg). The dose of these agents was determined by our preliminary studies (data not shown). Control diluent was given to the untreated control mice. Body weight and tumors were measured twice a week. Tumor sizes were calculated by the formula: a × b × c, where “a” is the length, “b” is the width, and “c” is the height in millimeters.

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In vivo studies. Male Swiss nude (nu/nu genotype), SCID-bg mice (CB17/Icr.Cg.PrkdcSCIDLystbg/Crl), or nude rats (Nude:Hsd Han:RNU-rnu; AstraZeneca) were housed in negative pressure isolators or in an individually ventilated cage system. Experiments were conducted on 8- to 12-week-old animals. Human tumor xenografts were established by s.c. injecting 100 to 200 μL tumor cells (between 1 × 106 and 1 × 107 cells mixed 50:50 with Matrigel; Becton Dickinson) on the flank. Animals were randomized into treatment groups (n = 8-11 per group) when tumors reached a defined palpable size (0.2-0.3 cm3 and 0.5-1 cm3 for mice and rats, respectively). AZD1152 was prepared in Tris buffer (pH 9) and administered either as a bolus injection (i.v. or i.p.) or as a continuous 48-h infusion via s.c. implanted osmotic mini-pumps (two 24-h pumps implanted sequentially.) in accordance with the manufacturer's instructions. Tumors were measured up to three times weekly with calipers, tumor volumes were calculated, and the data were plotted using the geometric mean for each group versus time. Tumor volume and tumor growth inhibition were calculated as described previously. Statistical analysis of any change in tumor volume was carried out using a Student's one-tailed t test (P value of <0.05 was considered to be statistically significant).[2]
For pharmacodynamic time course studies, nude rats bearing established SW620 tumor xenografts received vehicle or AZD1152 (25 mg/kg/d) as a daily i.v. bolus dose for 4 consecutive days (days 1-4). At multiple time points after dosing (days 0, 5, 9, 12, 16, and 19), two subgroups (n = 3 per group) of either vehicle- or AZD1152-treated animals were humanely killed and tumor and normal proliferating tissues (including bone marrow) were excised and assessed for pharmacodynamic effects using flow cytometric, histologic, or immunohistochemical analysis.[2]

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Female immune-deficient BALB/c nude mice (MOLM13 cells injected)[1].
5 or 25 mg/kg.
Intraperitoneal injection 4 times a week or every another day.

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MOLM13 Xenograft Model: Female immunodeficient BALB/c nude mice (4 weeks old) were subcutaneously injected bilaterally with MOLM13 leukemia cells (2x10⁶ cells/tumor) suspended in Matrigel. When palpable tumors formed, mice were randomized into treatment groups (n=5 mice/group, 10 tumors/group). [1]
AZD1152 Monotherapy: AZD1152 (formulated in 3 M Tris buffer, pH 9.0, at 2.5 mg/mL) was administered via intraperitoneal (i.p.) injection at doses of 5 or 25 mg/kg, four times a week for two weeks. Control mice received the diluent. [1]
Combination Therapy with Vincristine: AZD1152 (5 mg/kg, i.p., 4 times/week for 2 weeks) was co-administered with vincristine (0.2 mg/kg, i.p., every other day during the first week). [1]
Combination Therapy with Daunorubicin: AZD1152 (5 mg/kg, i.p., 4 times/week for 2 weeks) was co-administered with daunorubicin (1 mg/kg, i.p., 6 times over 2 weeks). [1]
Tumor dimensions (length, width, height) were measured twice weekly to calculate volume. Body weight was monitored as an indicator of toxicity. At the end of the experiment (2 weeks), mice were euthanized, tumors were excised and weighed, and tissue samples were collected for histological analysis. [1]

AZD1152 is described as a prodrug that is rapidly converted to its active metabolite, AZD1152-HQPA, in human plasma. [1]

In the mouse xenograft studies, no signs of wasting (body weight loss) or other overt toxicity were observed in mice treated with AZD1152 alone at 5 or 25 mg/kg. However, the combination regimen containing daunorubicin (1 mg/kg) was noted to be toxic, causing body weight loss in mice. [1]
The literature mentions that in phase I clinical trials (not part of this preclinical study's results), the dose-limiting toxicity of AZD1152 was neutropenia. [1]

[1]. 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]. 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.

[3]. The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma. Br J Haematol. 2008 Feb;140(3):295-302.

[4]. AZD1152 rapidly and negatively affects the growth and survival of human acute myeloid leukemia cells in vitro and in vivo. Cancer Res. 2009 May 15;69(10):4150-8.

AZT-1152 is a dihydrogen phosphate prodrug of a pyrazoloquinazoline aurora kinase inhibitor AZD1152-hydroxyquinazoline pyrazol anilide(HQPA) and is converted rapidly to the active AZD1152-HQPA in plasma. It has a role as a prodrug, an antineoplastic agent and an Aurora kinase inhibitor. It is a member of quinazolines, a monoalkyl phosphate, an anilide, a member of monofluorobenzenes, a member of pyrazoles, a secondary amino compound, a secondary carboxamide and a tertiary amino compound. It is functionally related to an AZD-1152.
Barasertib has been used in trials studying the treatment of Tumors, Lymphoma, Solid Tumors, Solid Tumours, and Myeloid Leukemia, among others.
Barasertib is an orally bioavailable, small-molecule, dihydrogen phosphate prodrug of the pyrazoloquinazoline Aurora kinase inhibitor AZD1152-hydroxyquinazoline pyrazol anilide (AZD1152-HQPA) with potential antineoplastic activity. Upon administration and rapid conversion from the prodrug form in plasma, AZD1152-HQPA specifically binds to and inhibits Aurora kinase B, which results in the disruption of spindle checkpoint functions and chromosome alignment and, so, the disruption of chromosome segregation and cytokinesis. Consequently, cell division and cell proliferation are inhibited and apoptosis is induced in Aurora kinase B-overexpressing tumor cells. Aurora kinase B, a serine/threonine protein kinase that functions in the attachment of the mitotic spindle to the centromere, is overexpressed in a wide variety of cancer cell types.

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\n\nAZD-1152 is a member of the of quinazolines that is 4-aminoquinazolin-7-ol in which the amino group at position 4 has been substituted by a 5-[2-(3-fluoroanilino)-2-oxoethyl]-1H-pyrazol-3-yl group, while the hydroxy group at position 7 has been converted into the corresponding 3-[ethyl(2-hydroxyethyl)aminopropyl ether. It has a role as an antineoplastic agent and an Aurora kinase inhibitor. It is a member of quinazolines, a secondary carboxamide, a tertiary amino compound, a secondary amino compound, a member of pyrazoles, a primary alcohol, a member of monofluorobenzenes and an anilide.
Defosbarasertib is a small-molecule inhibitor of the serine-threonine kinase Aurora B, with potential antineoplastic activity. Upon administration, defosbarasertib specifically binds to and inhibits Aurora kinase B, which disrupts spindle checkpoint functions and chromosome alignment, and results in the disruption of chromosome segregation and cytokinesis. This inhibits cell division and cell proliferation and induces apoptosis in Aurora kinase B-overexpressing tumor cells. Aurora kinase B, a serine/threonine protein kinase that functions in the attachment of the mitotic spindle to the centromere, is overexpressed in a wide variety of cancer cell types.

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\nAurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. We have recently shown that hematopoietic malignant cells including those from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) aberrantly expressed Aurora A and B kinases, and ZM447439, a potent inhibitor of Aurora kinases, effectively induced growth arrest and apoptosis of a variety of leukemia cells. The present study explored the effect of AZD1152, a highly selective inhibitor of Aurora B kinase, on various types of human leukemia cells. AZD1152 inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 nM to 40 nM, as measured by thymidine uptake on day 2 of culture. These cells had 4N/8N DNA content followed by apoptosis, as measured by cell-cycle analysis and annexin V staining, respectively. Of note, AZD1152 synergistically enhanced the antiproliferative activity of vincristine, a tubulin depolymerizing agent, and daunorubicin, a topoisomerase II inhibitor, against the MOLM13 and PALL-2 cells in vitro. Furthermore, AZD1152 potentiated the action of vincristine and daunorubicin in a MOLM13 murine xenograft model. Taken together, AZD1152 is a promising new agent for treatment of individuals with leukemia. The combined administration of AZD1152 and conventional chemotherapeutic agent to patients with leukemia warrants further investigation.\n[1]

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\nPurpose: In the current study, we examined the in vivo effects of AZD1152, a novel and specific inhibitor of Aurora kinase activity (with selectivity for Aurora B).\n\nExperimental design: The pharmacodynamic effects and efficacy of AZD1152 were determined in a panel of human tumor xenograft models. AZD1152 was dosed via several parenteral (s.c. osmotic mini-pump, i.p., and i.v.) routes.\n\nResults: AZD1152 potently inhibited the growth of human colon, lung, and hematologic tumor xenografts (mean tumor growth inhibition range, 55% to > or =100%; P < 0.05) in immunodeficient mice. Detailed pharmacodynamic analysis in colorectal SW620 tumor-bearing athymic rats treated i.v. with AZD1152 revealed a temporal sequence of phenotypic events in tumors: transient suppression of histone H3 phosphorylation followed by accumulation of 4N DNA in cells (2.4-fold higher compared with controls) and then an increased proportion of polyploid cells (>4N DNA, 2.3-fold higher compared with controls). Histologic analysis showed aberrant cell division that was concurrent with an increase in apoptosis in AZD1152-treated tumors. Bone marrow analyses revealed transient myelosuppression with the drug that was fully reversible following cessation of AZD1152 treatment.\n\nConclusions: These data suggest that selective targeting of Aurora B kinase may be a promising therapeutic approach for the treatment of a range of malignancies. In addition to the suppression of histone H3 phosphorylation, determination of tumor cell polyploidy and apoptosis may be useful biomarkers for this class of therapeutic agent. AZD1152 is currently in phase I trials.\n[2]

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\n\nProstate cancer is the frequent non-cutaneous tumor with high mortality in men. Prostate tumors contain cells with different status of androgen receptor. Androgen receptor plays important roles in progression and treatment of prostate cancer. Aurora B kinase, with oncogenic potential, is involved in chromosome segregation and cytokinesis, and its inhibition is a promising anti-cancer therapy. In the present study, we aimed to investigate the effects of Aurora B inhibitor, AZD1152-HQPA, on survival and proliferation of androgen receptor (AR)-positive prostate cancer cells. LNCaP was used as androgen-dependent prostate cancer cell line. We explored the effects of AZD1152-HQPA on cell viability, DNA content, micronuclei formation, and expression of genes involved in apoptosis and cell cycle. Moreover, the expression of Aurora B and AR were investigated in 23 benign prostatic hyperplasia and 38 prostate cancer specimens. AZD1152-HQPA treatment induced defective cell survival, polyploidy, and cell death in LNCaP cell line. Centromeric labeling with fluorescence in situ hybridization (FISH) showed that the loss of whole chromosomes is the origin of micronuclei, indicating on aneugenic action of AZD1152-HQPA. Treatment of AZD1152-HQPA decreased expression of AR. Moreover, we found weak positive correlations between the expression of Aurora B and AR in both benign prostatic hyperplasia and prostate cancer specimens (r = 0.25, r = 0.41). This is the first time to show that AZD1152-HQPA can be a useful therapeutic strategy for the treatment of androgen-dependent prostate cancer cell line. AZD1152-HQPA induces aneugenic mechanism of micronuclei production. Taken together, this study provides new insight into the direction to overcome the therapeutic impediments against prostate cancer.\n[3]

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\nAurora kinases play a critical role in regulating mitosis and cell division, and their overexpression has been implicated in the survival and proliferation of human cancer. In this study, we report the in vitro and in vivo activities of AZD1152, a compound that has selectivity for aurora B kinase, in acute myeloid leukemia (AML) cell lines, primary AML samples, and cord blood cells. AZD1152 exerted antiproliferative or cytotoxic effects in all cell lines studied, inhibited the phosphorylation of histone H3 (pHis H3) on Ser10 in a dose-dependent manner, and resulted in cells with >4N DNA content. THP-1 cells treated with AZD1152 accumulated in a state of polyploidy and showed a senescent response to the drug, in contrast to the apoptotic response seen in other cell lines. Accordingly, AZD1152 profoundly affected the growth of AML cell lines and primary AML in an in vivo xenotransplantation model. However, concentration-dependent effects on cell growth, apoptosis, and cell cycle progression were also observed when human cord blood and primary lineage-negative stem and progenitor cells were analyzed in vitro and in vivo. These data suggest that the inhibition of aurora B kinase may be a useful therapeutic strategy in the treatment of AML and that further exploration of dosing and treatment schedules is warranted in clinical trials.[4]\n

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AZD1152 is a novel acetanilide-substituted pyrazole-aminoquinazoline prodrug. Its active form, AZD1152-HQPA, is a highly potent and selective Aurora B kinase inhibitor, approximately 100-fold more potent than another Aurora kinase inhibitor, ZM447439, in leukemia cells. [1]
The mode of action involves inhibition of Aurora B kinase, leading to failure of cytokinesis, polyploidization (4N/8N DNA content), and subsequent apoptosis. [1]
It shows synergistic antitumor activity with conventional chemotherapeutic agents like vincristine and daunorubicin, both in vitro and in vivo. [1]
The study suggests AZD1152 may be a promising agent for treating leukemia, including cases resistant to imatinib, and warrants investigation in combination with other chemotherapies. [1]

C26H31FN7O6P

587.54

587.205

C, 53.15; H, 5.32; F, 3.23; N, 16.69; O, 16.34; P, 5.2 7

722543-31-9

Barasertib-HQPA;722544-51-6; 722543-31-9 (free acid); 722543-50-2 (2HCl); 957104-91-5

11497983

Off-white to light yellow solid powder

1.5±0.1 g/cm3

1.675

1.71

184.63

5

12

15

41

859

0

O=C(NC1=CC=CC(F)=C1)CC2=CC(NC3=C4C=CC(OCCCN(CC)CCOP(O)(O)=O)=CC4=NC=N3)=NN2

GBJVVSCPOBPEIT-UHFFFAOYSA-N

InChI=1S/C26H31FN7O6P/c1-2-34(10-12-40-41(36,37)38)9-4-11-39-21-7-8-22-23(16-21)28-17-29-26(22)31-24-14-20(32-33-24)15-25(35)30-19-6-3-5-18(27)13-19/h3,5-8,13-14,16-17H,2,4,9-12,15H2,1H3,(H,30,35)(H2,36,37,38)(H2,28,29,31,32,33)

2-[ethyl-[3-[4-[[5-[2-(3-fluoroanilino)-2-oxoethyl]-1H-pyrazol-3-yl]amino]quinazolin-7-yl]oxypropyl]amino]ethyl dihydrogen phosphate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.26 mM) (饱和度未知) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (4.26 mM) (饱和度未知) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.17 mg/mL (3.69 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 21.7 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 4 中的溶解度: ≥ 2.17 mg/mL (3.69 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，将100 μL 21.7 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 5 中的溶解度: ≥ 2.17 mg/mL (3.69 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 21.7 mg/mL澄清DMSO储备液加入900 μL玉米油中，混合均匀。

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配方 6 中的溶解度: 2% DMSO+40% PEG 300+2% Tween 80+ddH2O: 7mg/mL

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。