PF-03814735 is a potent, orally available, ATP-competitive and reversible aurora A and aurora B inhibitor with IC50s of 0.8 and 0.5 nM, respectively.
IC50&Target
Aurora 1
0.8 nM (IC50)
Aurora 2
5 nM (IC50)
Flt-1
10 nM (IC50)
FAK
22 nM (IC50)
TrkA
30 nM (IC50)
Met
100 nM (IC50)
FGFR1
100 nM (IC50)
体外研究
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.
体内研究
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.
分子式
C23H25N6O2F3
分子量
474.48
CAS号
942487-16-3
运输条件
Room temperature in continental US; may vary elsewhere.