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.

Physicochemical Properties

Molecular Formula	C20H19CLFN5OS
Molecular Weight	431.91
Exact Mass	431.098
CAS #	885325-71-3
Related CAS #	885325-71-3
PubChem CID	11676373
Appearance	White to yellow solid powder
Density	1.4±0.1 g/cm3
Boiling Point	605.5±65.0 °C at 760 mmHg
Flash Point	320.0±34.3 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.673
LogP	1.18
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	553
Defined Atom Stereocenter Count	0
InChi Key	YCRFPWKUUNKNDN-UHFFFAOYSA-N
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)
Chemical Name	(3-chloro-2-fluorophenyl)(4-((6-(thiazol-2-ylamino)pyridin-2-yl)methyl)piperazin-1-yl)methanone.
Synonyms	MK 8745; MK8745; MK-8745
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

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].
ln Vivo	NA
Animal Protocol	NA
References	[1]. The induction of polyploidy or apoptosis by the Aurora A kinase inhibitor MK8745 is p53-dependent. [2]. 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.

Solubility Data

Solubility (In Vitro)

DMSO: 86 mg/mL (199.1 mM) Water:<1 mg/mL Ethanol:1 mg/mL (2.3 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.