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Purity: ≥98%
MK-8745 is a novel, potent, specific and selective Aurora A inhibitor with potential antitumor activity. It inhibits Aurora A with an IC50 of 0.6 nM, and is 450-fold more selective for Aurora A over Aurora B. It shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy. Exposure of p53 wild-type cells to MK8745 resulted in the induction of p53 phosphorylation (ser15) and an increase in p53 protein expression. p53-dependent apoptosis by MK8745 was further confirmed in HCT 116 p53(-/-) cells transfected with wild-type p53.
| ln Vitro |
Tested in vitro on cell lines of various lineages, MK-8745 causes apoptotic cell death in a p53-dependent way. When MK-8745 is exposed to p53 wild-type cells, p53 phosphorylation (ser15) is induced and p53 protein expression rises[1]. All NHL cells undergo cell cycle arrest when exposed to 1 μM of MK-8745 for 24 hours, exhibiting varying degrees of G2/M arrest. Treatment with 1 μM MK-8745 causes a 5.5-fold rise in the G2/M phase cell population in 96 hours of highly sensitive Z138C cells. In Granta 519 and Z138C cells, MK-8745 administration suppresses the phosphorylation of Aurora-A; Akata and JVM2 had no impact. MK-8745 selectively blocks the function of Aurora -A. Treatment with MK-8745 causes apoptotic cell death[2].
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| References |
[1]. Jayasree S Nair et al. The induction of polyploidy or apoptosis by the Aurora A kinase inhibitor MK8745 is p53-dependent.
[2]. Aparajita Chowdhury et al. A novel Aurora kinase A inhibitor MK-8745 predicts TPX2 as a therapeutic biomarker in non-Hodgkin lymphoma cell lines. Leuk Lymphoma, 2012 Mar, 53(3):462-71 |
| Molecular Formula |
C20H19CLFN5OS
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| Molecular Weight |
431.91
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| CAS # |
885325-71-3
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| Related CAS # |
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| SMILES |
O=C(C1=CC=CC(Cl)=C1F)N2CCN(CC3=NC(NC4=NC=CS4)=CC=C3)CC2
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| InChi Key |
YCRFPWKUUNKNDN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19ClFN5OS/c21-16-5-2-4-15(18(16)22)19(28)27-10-8-26(9-11-27)13-14-3-1-6-17(24-14)25-20-23-7-12-29-20/h1-7,12H,8-11,13H2,(H,23,24,25)
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| Chemical Name |
(3-chloro-2-fluorophenyl)(4-((6-(thiazol-2-ylamino)pyridin-2-yl)methyl)piperazin-1-yl)methanone.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3153 mL | 11.5765 mL | 23.1530 mL | |
| 5 mM | 0.4631 mL | 2.3153 mL | 4.6306 mL | |
| 10 mM | 0.2315 mL | 1.1576 mL | 2.3153 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
MK8745 is a selective inhibitor of Aurora A kinase.Cell Cycle.2012 Feb 15;11(4):807-17. |
Cell cycle effect and induction of apoptosis by MK8745 (5 µM) in isogenic variants of HCT-116 cells (parental, p53−/−, p21−/−). (A) Flow cytometry analysis of the HCT 116 (top) and its isogenic variants; p21−/−(middle) and p53−/−(bottom) upon exposure to MK for different time points (6, 17, 22, 30 and 40 h) and exposure to ABI (100 nM AZD 1152) for 40 h after Propidium Iodide staining.Cell Cycle.2012 Feb 15;11(4):807-17. |
Downregulation of Aurora A recapitulates the effects of MK8745.Cell Cycle.2012 Feb 15;11(4):807-17. |
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