MK-8745 |
Catalog No.GC10442
One-Click Copy Product Info
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Aurora A inhibitor,potent and selective
Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| Chemical Name | (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 | ||
| Formula | C20H19ClFN5OS | M.Wt | 431.91 |
| Solubility | ≥ 21.6mg/mL in DMSO | Storage | Store at -20° C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3153 mL | 11.5765 mL | 23.153 mL |
| 5 mM | 463.1 μL | 2.3153 mL | 4.6306 mL |
| 10 mM | 231.5 μL | 1.1576 mL | 2.3153 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 6 reference(s) in Google Scholar.)