Molecular Formula | C23H25F3N6O2 |
Molar Mass | 474.48 |
Density | 1.443 |
Melting Point | 181-183°C |
Solubility | DMSO: soluble20mg/mL, clear |
Appearance | powder |
Color | white to beige |
pKa | 15.02±0.46(Predicted) |
Storage Condition | -20°C |
In vitro study | In intact cells, the inhibitory activity of PF-03814735 on the Aurora1 and Aurora2 kinases reduces levels of phospho-Aurora1, phosphohistone H3, and phospho-Aurora2. PF-03814735 produces a block in cytokinesis, resulting in inhibition of cell proliferation and the formation of polyploid multinucleated cells. Small cell lung cancer (SCLC) and, to a lesser extent, colon cancer lines are very sensitive to PF-03814735. The status of the Myc gene family and retinoblastoma pathway members significantly correlates with the efficacy of PF-03814735. |
In vivo study | Once-daily oral administration of PF-03814735 to mice bearing human xenograft tumors produces a reduction in phosphohistone H3 in tumors at doses that are tolerable and that result in significant inhibition of tumor growth. The combination of PF-03814735 and docetaxel in xenograft mouse tumor models shows additive tumor growth inhibition. PF-03814735 is much more effective in NCI-H82 xenografts when administered on a weekly dosing schedule at 80 mg/kg compared with a daily schedule at 15 mg/kg. PF-03814735 delayed growth by 23.5 days on the weekly schedule, which corresponds to 0.9 logs of net cell kill during the course of treatment. |
WGK Germany | 3 |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.108 ml | 10.538 ml | 21.076 ml |
5 mM | 0.422 ml | 2.108 ml | 4.215 ml |
10 mM | 0.211 ml | 1.054 ml | 2.108 ml |
5 mM | 0.042 ml | 0.211 ml | 0.422 ml |