PF-03814735

Cell lines

MDA-MB-231 cells, various tumor types (HCT-116, HL-60, A549, and H125) as well as tumor cell lines of rat (C6), mouse (L1210), and dog (MDCK) origin.

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.

Reacting condition

1-1000 nM; 4, 8, 12, 24, and 48 h

Applications

In MDA-MB-231 cells, PF-03814735 markedly reduced levels of Aurora1 phosphorylated on Thr 232 and the phosphorylation of histone H3 on Ser10 with IC50 values of 20 nmol/L and 50 nmol/L. In various tumor cell lines, PF-03814735 resulted in a reduction in cell number with IC50 values ranging from 42 to 150 nmol/L. PF-03814735 at 300 nmol/L produced near-complete inhibition of cell proliferation.

Animal models

Athymic mice bearing s.c. HCT-116 human colorectal cancer xenografts

Dosage form

10, 20, and 30 mg/kg; oral gavage for 10 days

Application

In athymic mice bearing s.c. HCT-116 human colorectal cancer xenografts, PF-03814735 (≥20 mg/kg) resulted in statistically significant and dose-dependent tumor growth inhibition of ≥50% relative to vehicle-treated mice. The tumor growth inhibition was associated with a reduction in phosphorylated histone H3 levels of ≥50% for approximately 5 hours each day for 10 days.

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] Jani JP, Arcari J, Bernardo V, Bhattacharya SK, Briere D, Cohen BD, Coleman K, Christensen JG, Emerson EO, Jakowski A, Hook K, Los G, Moyer JD, Pruimboom-Brees I, Pustilnik L, Rossi AM, Steyn SJ, Su C, Tsaparikos K, Wishka D, Yoon K, Jakubczak JL. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther. 2010 Apr;9(4):883-94.