PF-562271 Besylate

ArtNr	S2672-50
Hersteller	Selleckchem
CAS-Nr.	939791-38-5
Menge	50 mg
Quantity options	10 mg 100 mg 1 g 10 g 200 mg 5 mg 50 mg 500 mg 5 g
Kategorie	Oncology Neuroscience Neural Signaling Inhibitors & Compound Libraries Small Molecules By Organ Skin Cancer Colorectal Cancer Hepatic Cancer
Typ	Inhibitors
Specific against	other
Smiles	CN(C1=C(C=CC=N1)CNC2=NC(=NC=C2C(F)(F)F)NC3=CC4=C(C=C3)NC(=O)C4)S(=O)(=O)C.C1=CC=C(C=C1)S(=O)(=O)O
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	PF-00562271 Besylate
Similar products	PF-00562271
Lieferbar
Storage Conditions	2 years -80 in solvent
Molecular Weight	665, 66
Administration	Administered via p.o.
Animal Models	PC-3M, BT474, BxPc3, LoVo, U87MG, H125 and H460 cells are injected s.c. into the right flank of athymic female mice .
Cell lines	Squamous cell carcinoma (SCC)
Concentrations	0 to 1 uM
Dosages	<=100 mg/kg
Formulation	PF-562271 is dissolved in 5% Gelucire.
IC50	1.5 nM, 1.5 nM, 1.5 nM, 1.5 nM, 1.5 nM, 1.5 nM
In vitro	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. [1] 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 uM, 2.08 uM and 2.01 uM, respectively. [2]
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. [1] 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. [3] 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. [4]
Incubation Time	72 hours
Kinase Assay	Recombinant kinase assay and enzyme kinetics, Briefly, purified-activated FAK kinase domain (amino acid 410â€“689) is reacted with 50 uM ATP and 10 ug per well of a random peptide polymer of Glu and Tyr, p(Glu/Tyr), in kinase buffer [50 mM HEPES (pH 7.5), 125 mM NaCl, and 48 mM MgCl2] for 15 minutes. Phosphorylation of p(Glu/Tyr) is challenged with serially diluted PF-562271 at 1/2-Log concentrations starting at a top concentration of 1 uM. Each concentration is tested in triplicate. Phosphorylation of p(Glu/Tyr) is detected with a general antiphospho-tyrosine (PY20) antibody followed by horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG antibody. HRP substrate is added, and absorbance readings at 450 nm are obtained after addition of stop solution (2 M H2SO4). IC50 values are determined using the Hill-Slope Model. Broad kinase selectivity profiling is performed in house and by using the KinaseProfiler Selectivity Screening Service available through UpState Biotechnology.
Method	Cells 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.
Solubility (25C)	DMSO 0.4 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information	PF-562271 Besylate is the benzenesulfonate salt of PF-562271, which is a potent, ATP-competitive, reversible inhibitor of FAK with IC50 of 1.5 nM, ~10-fold less potent for Pyk2 than FAK and >100-fold selectivity against other protein kinases, except for some CDKs. Phase 1.
Chemical Name	N-methyl-N-(3-((2-(2-oxoindolin-5-ylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)methanesulfonamide benzenesulfonate

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