[CAS NO. 942487-16-3] PF-03814735
PRODUCTS SPECIFICATIONS [942487-16-3]
DESCRIPTION [942487-16-3]
Overview
| MDL | MFCD16659065 |
|---|---|
| Molecular Weight | 474.48 |
| Molecular Formula | C23H25F3N6O2 |
| SMILES | O=C(CNC(C)=O)N1[C@@H]2C3=C(C=C(NC4=NC(NC5CCC5)=C(C(F)(F)F)C=N4)C=C3)[C@H]1CC2 |
2 Publications Citing Use of MCE
Summary
IC50 & Target
|
Aurora 1 0.8 nM (IC 50 ) |
Aurora 2 5 nM (IC 50 ) |
Flt-1 10 nM (IC 50 ) |
FAK 22 nM (IC 50 ) |
TrkA 30 nM (IC 50 ) |
Met 100 nM (IC 50 ) |
FGFR1 100 nM (IC 50 ) |
In Vitro
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 [1] . 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 [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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 [1] . 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 [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00424632 | Pfizer |
Solid Tumors
|
November 2006 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 210.76 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.1076 mL | 10.5379 mL | 21.0757 mL |
| 5 mM | 0.4215 mL | 2.1076 mL | 4.2151 mL |
| 10 mM | 0.2108 mL | 1.0538 mL | 2.1076 mL |
References
- [1] Jani JP, et al. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther. 2010 Apr;9(4):883-94.
- [2] Hook KE, et al. An integrated genomic approach to identify predictive biomarkers of response to the aurora kinase inhibitor PF-03814735. Mol Cancer Ther. 2012 Mar;11(3):710-9.