MK-8745

Cell lines

Human non-Hodgkin lymphoma cell lines(NHL cell lines)

Preparation method

The solubility of this compound in DMSO is >21.6mg/mL. 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.

Reacting condition

1μM for 24 h and 48 h

Applications

In NHL cell lines, MK-8745 treatment for 48 h significantly decreased the cell number in TPX2 (targeting protein for Xenopus kinaselike protein 2) knockdown in cells in comparison to control cells. MK-8745 treatment induced an approximately 160-fold increase in cell death by 96 h and led to cell cycle arrest at the G2/M phase with accumulation of tetraploid nuclei followed by cell death in NHL cell lines.

Animal models

Female athymic mice at the age of 4 to 5 weeks (HCT116 isogenic cells were transplanted into both flanks of mice)

Dosage form

s.c, 800 nM for 7 to 12 days.

Application

Xenograft experiments indicated that MK-8745 showed anti-tumor activity, however, it did not regress tumors completely, and drug-resistant tumors still remained in mice. Tumor growth of HCT116 Puma(-), HCT116 p21(-), HCT116 Bax(-) and HCT116 Chk2(-) cells was significantly inhibited with MK-8745 in female athymic mice.

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]. Chowdhury, A., S. Chowdhury, M.Y., et al. Tsai, A novel Aurora kinase A inhibitor MK-8745 predicts TPX2 as a therapeutic biomarker in non-Hodgkin lymphoma cell lines. Leuk Lymphoma, 2012. 53(3): p. 462-71

[2]. Shionome, Y., et al. Integrity of p53 associated pathways determines induction of apoptosis of tumor cells resistant to Aurora-A kinase inhibitors. PLoS One, 2013. 8(1): p. e55457.