巴拉塞替作用机制 - Medchemexpress - MCE中国

1、Product Data SheetAZD1152Cat. No.: HY-10127CAS No.: 722543-31-9分式: CHFNOP分量: 587.54作靶点: Aurora Kinase作通路: Cell Cycle/DNA Damage; Epigenetics储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 33 mg/mL (56.17 mM)* means soluble, but saturation unknown.SolventMass1 m

2、g 5 mg 10 mgConcentration制备储备液1 mM 1.7020 mL 8.5101 mL 17.0201 mL5 mM 0.3404 mL 1.7020 mL 3.4040 mL10 mM 0.1702 mL 0.8510 mL 1.7020 mL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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按

3、照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.17 mg/mL (3.69 mM); Clear solution此案可获得 2.17 mg/mL (3.69 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 10

4、0 L 21.7 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.17 mg/mL (3.69 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.17 mg/mL (3.69 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 21.7 mg/mL 的澄 DMSO 储备液加

5、到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.17 mg/mL (3.69 mM); Clear solution此案可获得 2.17 mg/mL (3.69 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 21.7 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 AZD1152Barasertib-hQPA 的前体药物， 度选择性的 Aurora B

6、抑制剂，IC50 值为 0.37 nM。IC & Target Aurora B0.37 nM (IC50)体外研究 AZD1152 displays 3000-fold selectivity for Aurora B as compared with Aurora A which has an IC50 of 1.368 M.AZD1152 has even less activity against 50 other serine-threonine and tyrosine kinases including FLT3, JAK2, and Abl.AZD1152 inhibits t

7、he 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 appr 100-fold potency than another Aurorakinase inhibitor ZM334739 which has IC50 of 3-30 M. AZD1152 inhibits the clonogenic growth of MO

8、LM13 andMV4-11 cells with IC50 of 1 nM and 2.8 nM, respectively, as well as the freshly isolated imatinib-resistant leukemiacells with IC50 values of 1-3 nM, more significantly compared with bone marrow mononuclear cells with IC50 values of10 nM. AZD1152 induces accumulation of cells with 4N/8N DNA

9、content, followed by apoptosis in a dose- andtime-dependent manner1. AZD1152 causes significant accumulation of cells with 4N/8N DNA content in KMS12 andU266 and induces apoptosis in KMS18 and U266. AZD1152 in combination with DEX, has negative effects on cellviability in comparison with single agen

10、t in PMI8226, KMS11 and U2663.体内研究 Administration of AZD1152 (25 mg/kg) alone markedly suppresses the growth of MOLM13 xenografts, confirmed bythe observation of necrotic tissue with infiltration of phagocytic cells1. In addition, AZD1152 (10-150 mg/kg/day)significantly inhibits the growth of a vari

11、ety of human solid tumor xenografts, including colon, breast, and lungcancers, in a dose-dependent manner2. AZD1152 (25 mg/kg/day) treatment reduces xenograft levels such that theyare slightly lower levels than after the first round of treatment, but this is not statistically significant indicating

12、thatresidual cells might be more resistant to a second cycle of AZD11524.PROTOCOLCell Assay 3 Approximately 1105 cells in RPMI media with 10% FBS media are plated per well in a treated 96-well plate at 24-hintervals for up to 120 h (in triplicate for each time-point). For each timepoint, 20 L of MTS

13、 reagent 3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt solution is added toeach well and incubated at 37C for 4 h. The plate absorbance is read at 490 nm on a 96-well spectra max 190 PlateReader using Softmax Pro 4.8 Software. MTS solution is ad

14、ded to media-only wells to correct for background. Settingthe control cells at 100% viability, the viability of cells treated with various concentrations of siRNA or drug isdetermined and graphed using MS Excel.MCE has not independently confirmed the accuracy of these methods. They are for reference

15、 only.Animal Female immune-deficient BALB/c nude mice at 4 weeks of age are purchased from JAPAN SLC and are maintained inAdministration 1 pathogen-free conditions with irradiated chow. Animals are bilaterally, subcutaneously injected with 2106 MOLM13Page 2 of 3 www.MedChemEcells/tumor in 0.1 mL Mat

16、rigel. When MOLM13 cells formed palpable tumors, mice are divided randomLy into control(n=5) and treatment groups (n=5), and treatment is begun. AZD1152 (5 or 25 mg/kg) with or without vincristine (0.2mg/kg) is given to mice by intraperitoneal injection 4 times a week or every another day, respectiv

17、ely. Daunorubicin(1 mg/kg) is given to mice by intraperitoneal injection 6 times during 2 weeks of treatment either alone or incombination with AZD1152 (5 mg/kg). The dose of these agents is determined by our preliminary studies. Controldiluent is given to the untreated control mice. Body weight and

18、 tumors are measured twice a week. Tumor sizes arecalculated. At the end of the experiment, animals are killed by CO2 asphyxiation and tumor weights are measuredafter their careful resection. Tumor tissue is collected for analysis.MCE has not independently confirmed the accuracy of these methods. Th

19、ey are for reference only.户使本产品发表的科研献 Science. 2017 Dec 1;358(6367). pii: eaan4368. Nat Commun. 2019 Apr 18;10(1):1812 Clin Cancer Res. 2019 Jul 15;25(14):4552-4566. Patent. US20180263995A1. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK www.MedChemE www.MedChemEREFER

20、ENCES1. Yang J, et al. AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizingagent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood. 2007 Sep2. Wilkinson RW, et al. AZD1152, a selective inhibitor of Aurora B kinase, i