Cell lines

Tumor cell types (HCT116, LS174T, HL60, MDA-MB-231, ZR-75-1, MCF-7, PC3, MIA PaCa2, A375 and HeLa).

Preparation method

The solubility of this compound in DMSO is >10 mM. 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.

Reaction Conditions

48 h; IC50(15 nM-113 nM)

Applications

VX-680 caused accumulation of cells with 4 N DNA content and potently inhibited the proliferation of a wide variety of tumor cell types with half-maximal inhibitory concentration (IC50) values ranging from 15 to 113 nM. These data are consistent with the prediction that the Aurora kinases are crucial for cell-cycle progression, and with the finding that overexpression of kinase-inactive Aurora-B disrupts cell division.

Animal models

Female athymic NCr-nu mice

Dosage form

75 mg/kg; b.i.d.i.p.

Applications

VX-680 caused a marked reduction in tumor size in a human AML (HL-60) xenograft model. In nude mice treated with VX-680 at 75 mg/kg, twice a day intraperitoneally (b.i.d.i.p.) for 13 d, mean tumor volumes were reduced by 98% (P < 0.001) in comparison with the control group.

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.

MK-5108, also known as VX-689, is a novel, potent and selective inhibitor of Aurora A kinase (AAK) that competitively binds to the ATP binding site of AAK and hence potently inhibits the activity of AAK with 50% inhibition concentration IC₅₀value of 0.064 nM. MK-5108 also inhibits other members of Aurora kinase family, including Aurora B kinase (IC₅₀= 14 nM) and Aurora C kinase (IC₅₀= 12 nM), with a lesser potency. MK-5108 has been extensively studies and found to exhibit antitumor activity in a wide range of cancer types, including breast, cervix, colorectal, ovary and pancreas neoplasms.

Reference

[1].Myke R. Green, BS, Pharm.D., BCOP, Joseph E. Woolery, BS, Pharm.D, and Daruka Mahadevan, MD, PhD. Update on Aurora Kinase Targeted Therapeutics in Oncology. Recent Pat Anticancer Drug Discov. 2008 November ; 3(3): 162–177.