MK-5108 (also known as VX-689) is a novel, specific and ATP-competitive inhibitor of Aurora A kinase with potential anticancer activity. It inhibits Aurora A kinase with an IC50 of 0.064 nM in a cell-free assay. MK-5108 also less potently inhibits other Aurora kinases, including Aurora B kinase (IC50 = 14 nM) and Aurora C kinase (IC50 = 12 nM). MK-5108 has been found to exhibit antitumor activity in a wide range of cancer types, including breast, cervix, colorectal, ovary and pancreas neoplasms.

Physicochemical Properties

Molecular Formula	C22H21CLFN3O3S
Molecular Weight	461.94
Exact Mass	461.097
CAS #	1010085-13-8
Related CAS #	1010085-13-8
PubChem CID	24748204
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	637.6±65.0 °C at 760 mmHg
Flash Point	339.4±34.3 °C
Vapour Pressure	0.0±2.0 mmHg at 25°C
Index of Refraction	1.651
LogP	4.58
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	31
Complexity	611
Defined Atom Stereocenter Count	0
InChi Key	LCVIRAZGMYMNNT-VVONHTQRSA-N
InChi Code	InChI=1S/C22H21ClFN3O3S/c23-16-4-2-5-17(19(16)24)30-15-7-9-22(10-8-15,20(28)29)13-14-3-1-6-18(26-14)27-21-25-11-12-31-21/h1-6,11-12,15H,7-10,13H2,(H,28,29)(H,25,26,27)/t15-,22-
Chemical Name	(1r,4r)-4-(3-chloro-2-fluorophenoxy)-1-((6-(thiazol-2-ylamino)pyridin-2-yl)methyl)cyclohexane-1-carboxylic acid
Synonyms	VX-689; VX689; VX 689; MK5108; MK-5108; MK 5108; VX-689
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	MK-5108 has an IC50 value of 0.064 nM and inhibits Aurora-A activity in an ATP-competitive manner. Compared to the other family circuits, Aurora-B (220-fold) and Aurora-C (190-fold), it demonstrated stronger switching. The selectivity of MK-5108 towards Aurora-A is also interfered with by other proteins. 14 cell lines are inhibited in growth by MK-5108, with IC50 values ranging from 0.16 to 6.4 μM [1].
ln Vivo	In the HCT116 tumor model, MK-5108 therapy at 15 and 30 mg/kg significantly inhibited tumor growth. MK-5108 caused little weight loss and was well tolerated at both dosages. Significant anti-tumor efficacy was also demonstrated by MK-5108 in nude mice with SW48 tumors. Tumor growth inhibition was dose-dependent and produced %T/C of 35% and 7% on day 10 and 58% and 32% on day 27 at 15 and 45 mg/kg of MK-5108, respectively. In naked mice, MK-5108 was well tolerated, causing little weight loss and only mild effects on blood cells [1].
Animal Protocol	Dissolved in 0.5% methyl cellulose/0.24% SDS; 30 mg/kg; Oral gavage. SCID mice bearing HCT116 tumors
References	[1]. MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Mol Cancer Ther. 2010 Jan;9(1):157-66.
Additional Infomation	4-(3-chloro-2-fluorophenoxy)-1-[[6-(2-thiazolylamino)-2-pyridinyl]methyl]-1-cyclohexanecarboxylic acid is an aromatic ether. MK-5108 has been used in trials studying the treatment of Cancer, Neoplasms, Tumors. Aurora A Kinase Inhibitor MK5108 is an orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A, with potential antimitotic and antineoplastic activity. Aurora A kinase inhibitor MK5108 binds to and inhibits Aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and eventually inhibition of cell division, proliferation and an induction of apoptosis in cells overexpressing Aurora A kinase. Aurora A kinase localizes to the spindle poles and to spindle microtubules during mitosis, and is thought to regulate spindle assembly. Aurora kinases are overexpressed in a wide variety of cancers.

Solubility Data

Solubility (In Vitro)

DMSO: 92 mg/mL (199.1 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (2.71 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 12.5 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: ≥ 1.25 mg/mL (2.71 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 12.5 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: ≥ 1.25 mg/mL (2.71 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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 0.5% methylcellulose+0.2% Tween 80:~30mg/mL Solubility in Formulation 5: 6.67 mg/mL (14.44 mM) in 0.5% MC 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1648 mL	10.8239 mL	21.6478 mL
	5 mM	0.4330 mL	2.1648 mL	4.3296 mL
	10 mM	0.2165 mL	1.0824 mL	2.1648 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.