product name PF-00562271
Description: PF-00562271 (also known as PF-562271 or PF-562271 Besylate), the benzenesulfonate salt of PF-562271, is a potent, orally bioavailable, ATP-competitive, reversible inhibitor of FAK with IC50 of 1.5 nM, it has >100-fold selectivity against other protein kinases. As a potential therapeutic agent either alone or in combination with other agents for the treatment of cancer, PF-562271 has been reported to effectively inhibit the proliferation of tumors in both xenograft and transgenic mouse models.
References: Cancer Res. 2008 Mar 15;68(6):1935-44; Cancer Biol Ther. 2010 Jul 1;10(1):38-43.
665.66
Formula
C21H20F3N7O3S.C6H6O3S
CAS No.
939791-38-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 14 mg/mL (21.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
4% DMSO+30% PEG 300+ddH2O: 3 mg/mL
Synonyms
PF-562271 or PF-562271 Besylate
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19420092
| In Vitro |
In vitro activity: PF-562271 shows the selective inhibitory effects on FAK and Pyk2 tyrosine kinase activity with IC50 of 1.5 nM and 14 nM, respectively. And in cell-based assays, the IC50 of PF-562271 is shown to be 5 nM for FAK, which is more selective compared to other kinase targets. In 2 dimensional (2D) cultures, PF-562271 results in a dose-dependent cell proliferation inhibition in FAK WT, FAK−/− and FAK kinase-deficient (KD) cells with IC50 of 3.3 μM, 2.08 μM and 2.01 μM, respectively. Kinase Assay: PF-562271 shows the selective inhibitory effects on FAK and Pyk2 tyrosine kinase activity with IC50 of 1.5 nM and 14 nM, respectively. And in cell-based assays, the IC50 of PF-562271 is shown to be 5 nM for FAK, which is more selective compared to other kinase targets. In 2 dimensional (2D) cultures, PF-562271 results in a dose-dependent cell proliferation inhibition in FAK WT, FAK−/− and FAK kinase-deficient (KD) cells with IC50 of 3.3 μM, 2.08 μM and 2.01 μM, respectively. Cell Assay: Cells (Squamous cell carcinoma (SCC) are plated for 48 hours before addition of PF-562271. After 3 days cells are fixed by addition of ice cold 25% trichloroacetic acid (TCA) solution prior to staining with Sulforhodamine B (SRB) dye solution. Plates are washed with 1% glacial acetic acid, air-dried and resuspended in 10 mM Tris buffer, pH 10.5 before reading absorbance at 540 nm. Curve fitting and generation of IC50 values is carried out using GraphPad Prism 4 software from six replicates. |
|---|---|
| In Vivo | In several human s.c. xenograft models, PF-562271 exhibits dose-dependent tumor growth inhibition, and produces maximum tumor inhibition for PC-3M, BT474, BxPc3, and LoVo ranging from 78% to 94% inhibition at doses of 25 to 50 mg/kg twice daily, without weight loss, morbidity, or death. PF-562271 (25 mg/kg by p.o.) leads to a significant decrease in tumor progression in both subcutaneous and bone metastasis PC3M-luc-C6 xenograft models. In a Huh7.5 hepatocellular carcinoma xenograft model, combination therapy of sunitinib and PF-562271 targets angiogenesis and tumor aggressiveness, and produces more significant anti-tumor effect than single agent by blocking tumor growth and impacting the ability of the tumor to recover upon withdrawal of the therapy. |
| Animal model | PC-3M, BT474, BxPc3, LoVo, U87MG, H125 and H460 cells are injected s.c. into the right flank of athymic female mice |
| Formulation & Dosage | Dissolved in in 5% Gelucire; 100 mg/kg; Oral gavage |
| References | Cancer Res. 2008 Mar 15;68(6):1935-44; Cancer Biol Ther. 2010 Jul 1;10(1):38-43. |
