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AZD1152-HQPA(Barasertib)

产品号 S1147 公司名称 Selleck Chemicals
CAS号 722544-51-6 公司网站 http://www.selleckchem.com
分子式 C26H30FN7O3 电 话 (877) 796-6397
分子量 507.5599032 传 真 (832) 582-8590
纯 度 电子邮件 sales@selleckchem.com
保 存 -20°C Chembase数据库ID: 72543

产品价格信息

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产品别名

标题
AZD1152-HQPA(Barasertib)
IUPAC标准名
2-{5-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-3-yl}-N-(3-fluorophenyl)acetamide
IUPAC传统名
2-{5-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-3-yl}-N-(3-fluorophenyl)acetamide
别名
Barasertib

产品登记号

CAS号 722544-51-6

产品性质

作用靶点 Aurora Kinase
成盐信息 Free Base
溶解度 DMSO
保存条件 -20°C

产品详细信息

详细说明 (English)
Research Area
Description Cancer
Biological Activity
Description AZD1152-HQPA (Barasertib) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM.
Targets Aurora B
IC50 0.37 nM [1]
In Vitro AZD1152 displays >3000-fold selectivity for Aurora B as compared with Aurora A which has an IC50 of 1.368 μM. AZD1152 has even less activity against 50 other serine-threonine and tyrosine kinases including FLT3, JAK2, and Abl. AZD1152 inhibits the proliferation of hematopoietic malignant cells such as HL-60, NB4, MOLM13, PALL-1, PALL-2, MV4-11, EOL-1, THP-1, and K562 cells with IC50 of 3-40 nM, displaying ~100-fold potency than another Aurora kinase inhibitor ZM334739 which has IC50 of 3-30 μM. AZD1152 inhibits the clonogenic growth of MOLM13 and MV4-11 cells with IC50 of 1 nM and 2.8 nM, respectively, as well as the freshly isolated imatinib-resistant leukemia cells with IC50 values of 1-3 nM, more significantly compared with bone marrow mononuclear cells with IC50 values of >10 nM. AZD1152 induces accumulation of cells with 4N/8N DNA content, followed by apoptosis in a dose- and time-dependent manner. [1]
In Vivo Administration of AZD1152 (25 mg/kg) alone markedly suppresses the growth of MOLM13 xenografts, confirmed by the observation of necrotic tissue with infiltration of phagocytic cells. [1] In addition, AZD1152 (10-150 mg/kg/day) significantly inhibits the growth of a variety of human solid tumor xenografts, including colon, breast, and lung cancers, in a dose-dependent manner. [2]
Clinical Trials A Phase I study to assess the safety and tolerability of AZD1152-HQPA in combination with low dose cytosine arabinoside (LDAC) in patients with acute myeloid leukaemia (AML) has been completed.
Features
Combination Therapy
Description AZD1152 (3 nM) synergistically enhances the antiproliferative activity of conventional antileukemia agent vincristine (0.3 μM) or daunorubicin against the MOLM13 and PALL-2 cells, with the increased inhibition from 35% in vincristine alone to 80% in combination, which is consistent with the augmented cleavage of PARP. [1] AZD1152 (5 mg/kg) in combination with vincristine (0.2 mg/kg) or daunorubicin (1 mg/kg) completely inhibits the proliferation of human MOLM13 leukemic xenografts, more potently than that of any drug treatment alone with inhibition only by ~50%. [1]
Protocol
Cell Assay [1]
Cell Lines HL-60, NB4, MOLM13, PALL-2, MV4-11, EOL-1, and K562 cells
Concentrations Dissolved in DMSO, final concentrations ~100 nM
Incubation Time 24 or 48 hours
Methods Cells are exposed to various concentrations of AZD1152 for 24 or 48 hours. Cell proliferation is measured by 3H-thymidine uptake (isotope added 6 hours before harvest), and the concentration that induced 50% growth inhibition (IC50) is calculated from dose-response curves. Cell cycle analysis is performed by flow cytometry. Cell apoptosis is measured by annexin V–FITC apoptosis detection kit.
Animal Study [1]
Animal Models Female immune-deficient BALB/c nude mice subcutaneously injected with MOLM13 cells
Formulation Dissolved in 3M Tris, pH 9.0, at a concentration of 2.5 mg/mL
Doses 5 or 25 mg/kg
Administration Intraperitoneal injection 4 times a week or every another day
References
[1] Yang J, et al. Blood, 2007, 110(6), 2034-2040.
[2] Wilkinson RW, et al. Clin Cancer Res, 2007, 13(12), 3682-3688.