MK-5108 (VX-689) (Synonyms: VX-689)

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 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C 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.

References:

[1] Harrington E A, Bebbington D, Moore J, et al. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo[J]. Nature medicine, 2004, 10(3): 262-267.