product name PF-562271 HCl
Description: PF-562271 HCl is the hydrochloride salt of PF-562271, which is a potent, orally bioavailable, ATP-competitive, reversible inhibitor of FAK with IC50 of 1.5 nM, it is about 10-fold less potent for Pyk2 than FAK and >100-fold selectivity against other protein kinases, except for some CDKs. PF-562271 inhibits the tyrosine kinase FAK, and to a lesser extent, proline-rich tyrosine kinase (PYK2), which may inhibit tumor cell migration, proliferation, and survival.
References: Cancer Res. 2008 Mar 15;68(6):1935-44; Cancer Biol Ther. 2010 Jul 1;10(1):38-43.
543.95
Formula
C21H21ClF3N7O3S
CAS No.
939791-38-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (183.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19420159
| In Vitro |
In vitro activity: PF-562271 binds in the ATP-binding cleft of FAK, forming two of the three “canonical” H-bonds between the inhibitor and main-chain atoms in the kinase hinge region. PF-562271 is potent in an inducible cell-based assay measuring phospho-FAK with IC50 of 5 nM. PF-562271 (3.3 μM) results in G1 arrest of PC3-M cells. PF-562271 (1 nM) blocks bFGF-stimulated blood vessel angiogenesis as performed in chicken chorioallantoic membrane assays. PF-262271 potently blocks blood vessel sprouting without detectable changes in vascular leakage. PF-562271 (250 nM) results in complete inhibition of collective A431 cell invasion into collagen gels. 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 | PF-562271 (< 33 mg/kg p.o.) inhibits FAK phosphorylation in tumors in a dose- and time-dependent manner in U87MG-bearing mice. PF-562271 (50 mg/kg p.o. bid) results in 86% tumor growth inhibition in BxPc3 xenografts mice and 45% tumor growth inhibition in PC3-M xenografts mice. PF-562271 (25 mg/kg, bid) results in 2-fold greater apoptosis in treated tumors in mice bearing H125 lung xenografts. PF-562271 (33 mg/kg, p.o.) inhibits extensive movement of the tumor cells over 24 hours in mice. PF-562271 (33 mg/kg, p.o.) results in altered E-cadherin dynamics in mice, which correlates with reduced E-cadherin–dependent collective cell movement. PF-562271 (25 mg/kg, p.o. bid) results in 62% tumor growth inhibition in PC3M-luc-C6 subcutaneuous local implant xenograft mouse model. PF-562,271 (5 mg/kg, oral) results in significant and similar increases in osteocalcin and cancellous bone parameters and a decrease in tumor growth and signs of bone healing in rats implanted with MDA-MB-231 cells in the tibia. |
| Animal model | Athymic female mice bearing BxPc3 or PC3-M xenografts. |
| 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. |
