MK-8745
目录号 : GC10442
An Aurora A kinase inhibitor
Cas No.:885325-71-3
Sample solution is provided at 25 µL, 10mM.
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MK-8745 is a novel and selective inhibitor of Aurora A with IC50 value of 0.6 nM [1].
Aurora A kinase is a member of mitotic serine/threonine kinases and plays an important role in cellular division by controlling chromatid segregation. It has been reported that abnormal expression of Aurora A is correlated with the high occurrence of cancer and its expression determines cell sensitivity to MK-8745 treatment [1].
MK-8745 is a potent Aurora A inhibitor. When tested with p53-/+ cell lines, MK-8745 treatment induced apoptotic cell death in a p53-dependent manner through inhibiting Aurora A activity [1]. In non-Hodgkin lymphoma (NHL) cell lines, MK-8745 treatment arrested cell cycle in G2/M phase and induced cell death via inhibiting Aurora A kinase [2]. In HCT 116 Puma (-), HCT116 p21 (-), HCT116 Bax(-) and HCT116 Chk2(-) cell lines, MK-8745 treatment induced cell apoptosis with the percent of 25%, 22%, 25%, and 22%, respectively [3].
In female athymic nude mice model subcutaneous xenografted with HCT116 Puma (-), HCT116 p21 (-), HCT116 Bax(-) and HCT116 Chk2(-) cells, administration of MK-8745 significantly inhibited tumor growth [3].
References:
[1]. Nair, J.S., A.L. Ho, and G.K. Schwartz, The induction of polyploidy or apoptosis by the Aurora A kinase inhibitor MK8745 is p53-dependent. Cell Cycle, 2012. 11(4): p. 807-17.
[2]. Chowdhury, A., S. Chowdhury, and M.Y. Tsai, A novel Aurora kinase A inhibitor MK-8745 predicts TPX2 as a therapeutic biomarker in non-Hodgkin lymphoma cell lines. Leuk Lymphoma, 2012. 53(3): p. 462-71.
[3]. Shionome, Y., et al., Integrity of p53 associated pathways determines induction of apoptosis of tumor cells resistant to Aurora-A kinase inhibitors. PLoS One, 2013. 8(1): p. e55457.
| Cell experiment [1]: | |
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Cell lines |
Human non-Hodgkin lymphoma cell lines(NHL cell lines) |
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Preparation method |
The solubility of this compound in DMSO is >21.6mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1μM for 24 h and 48 h |
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Applications |
In NHL cell lines, MK-8745 treatment for 48 h significantly decreased the cell number in TPX2 (targeting protein for Xenopus kinaselike protein 2) knockdown in cells in comparison to control cells. MK-8745 treatment induced an approximately 160-fold increase in cell death by 96 h and led to cell cycle arrest at the G2/M phase with accumulation of tetraploid nuclei followed by cell death in NHL cell lines. |
| Animal experiment [2]: | |
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Animal models |
Female athymic mice at the age of 4 to 5 weeks (HCT116 isogenic cells were transplanted into both flanks of mice) |
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Dosage form |
s.c, 800 nM for 7 to 12 days. |
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Application |
Xenograft experiments indicated that MK-8745 showed anti-tumor activity, however, it did not regress tumors completely, and drug-resistant tumors still remained in mice. Tumor growth of HCT116 Puma(-), HCT116 p21(-), HCT116 Bax(-) and HCT116 Chk2(-) cells was significantly inhibited with MK-8745 in female athymic mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Chowdhury, A., S. Chowdhury, M.Y., et al. Tsai, A novel Aurora kinase A inhibitor MK-8745 predicts TPX2 as a therapeutic biomarker in non-Hodgkin lymphoma cell lines. Leuk Lymphoma, 2012. 53(3): p. 462-71 [2]. Shionome, Y., et al. Integrity of p53 associated pathways determines induction of apoptosis of tumor cells resistant to Aurora-A kinase inhibitors. PLoS One, 2013. 8(1): p. e55457. | |
| Cas No. | 885325-71-3 | SDF | |
| 化学名 | (3-chloro-2-fluorophenyl)(4-((6-(thiazol-2-ylamino)pyridin-2-yl)methyl)piperazin-1-yl)methanone | ||
| Canonical SMILES | ClC1=C(F)C(C(N2CCN(CC3=NC(NC4=NC=CS4)=CC=C3)CC2)=O)=CC=C1 | ||
| 分子式 | C20H19ClFN5OS | 分子量 | 431.91 |
| 溶解度 | ≥ 21.6mg/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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3153 mL | 11.5765 mL | 23.153 mL |
| 5 mM | 0.4631 mL | 2.3153 mL | 4.6306 mL |
| 10 mM | 0.2315 mL | 1.1576 mL | 2.3153 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
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet