Home Angiogenesis FAK inhibitor - Pyk2 inhibitor - CDK inhibitor PF-562271 Besylate For research use only.

PF-562271 Besylate

Synonyms: PF-00562271 Besylate

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.

PF-562271 Besylate Chemical Structure

PF-562271 Besylate Chemical Structure

CAS No. 939791-38-5

Purity & Quality Control

PF-562271 Besylate Related Products

Signaling Pathway

FAK Signaling Pathways

FAK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MV-4-11 cell Growth inhibition assay Inhibition of human MV-4-11 cell growth in a cell viability assay, IC50=0.2766 μM SANGER
human SW982 cell Growth inhibition assay Inhibition of human SW982 cell growth in a cell viability assay, IC50=0.3282 μM SANGER
human KM12 cell Growth inhibition assay Inhibition of human KM12 cell growth in a cell viability assay, IC50=0.38557 μM SANGER
human COLO-205 cell Growth inhibition assay Inhibition of human COLO-205 cell growth in a cell viability assay, IC50=0.48658 μM SANGER
human COLO-829 cell Growth inhibition assay Inhibition of human COLO-829 cell growth in a cell viability assay, IC50=0.76176 μM SANGER
human MG-63 cell Growth inhibition assay Inhibition of human MG-63 cell growth in a cell viability assay, IC50=0.80637 μM SANGER
human IGROV-1 cell Growth inhibition assay Inhibition of human IGROV-1 cell growth in a cell viability assay, IC50=0.81038 μM SANGER
human NCI-H650 cell Growth inhibition assay Inhibition of human NCI-H650 cell growth in a cell viability assay, IC50=0.83154 μM SANGER
human RT-112 cell Growth inhibition assay Inhibition of human RT-112 cell growth in a cell viability assay, IC50=0.9846 μM SANGER
human BCPAP cell Growth inhibition assay Inhibition of human BCPAP cell growth in a cell viability assay, IC50=1.01288 μM SANGER
ALL-PO cell Growth inhibition assay Inhibition of human ALL-PO cell growth in a cell viability assay, IC50=1.01584 μM SANGER
human KYSE-270 cell Growth inhibition assay Inhibition of human KYSE-270 cell growth in a cell viability assay, IC50=1.04714 μM SANGER
human 8305C cell Growth inhibition assay Inhibition of human 8305C cell growth in a cell viability assay, IC50=1.09904 μM SANGER
NCI-H810 cell Growth inhibition assay Inhibition of human NCI-H810 cell growth in a cell viability assay, IC50=1.10776 μM SANGER
human CAL-33 cell Growth inhibition assay Inhibition of human CAL-33 cell growth in a cell viability assay, IC50=1.12938 μM SANGER
human AN3-CA cell Growth inhibition assay Inhibition of human AN3-CA cell growth in a cell viability assay, IC50=1.21867 μM SANGER
human NKM-1 cell Growth inhibition assay Inhibition of human NKM-1 cell growth in a cell viability assay, IC50=1.27506 μM SANGER
human BPH-1 cell Growth inhibition assay Inhibition of human BPH-1 cell growth in a cell viability assay, IC50=1.28766 μM SANGER
human MES-SA cell Growth inhibition assay Inhibition of human MES-SA cell growth in a cell viability assay, IC50=1.30682 μM SANGER
human CAL-62 cell Growth inhibition assay Inhibition of human CAL-62 cell growth in a cell viability assay, IC50=1.31909 μM SANGER
human KYSE-150 cell Growth inhibition assay Inhibition of human KYSE-150 cell growth in a cell viability assay, IC50=1.35236 μM SANGER
human SK-UT-1 cell Growth inhibition assay Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=1.44647 μM SANGER
human HUTU-80 cell Growth inhibition assay Inhibition of human HUTU-80 cell growth in a cell viability assay, IC50=1.44886 μM SANGER
human SIG-M5 cell Growth inhibition assay Inhibition of human SIG-M5 cell growth in a cell viability assay, IC50=1.48487 μM SANGER
human AGS cell Growth inhibition assay Inhibition of human AGS cell growth in a cell viability assay, IC50=1.52124 μM SANGER
human ST486 cell Growth inhibition assay Inhibition of human ST486 cell growth in a cell viability assay, IC50=1.53278 μM SANGER
human HSC-2 cell Growth inhibition assay Inhibition of human HSC-2 cell growth in a cell viability assay, IC50=1.5395 μM SANGER
human BC-1 cell Growth inhibition assay Inhibition of human BC-1 cell growth in a cell viability assay, IC50=1.61664 μM SANGER
human CGTH-W-1 cell Growth inhibition assay Inhibition of human CGTH-W-1 cell growth in a cell viability assay, IC50=1.61679 μM SANGER
human MZ1-PC cell Growth inhibition assay Inhibition of human MZ1-PC cell growth in a cell viability assay, IC50=1.62312 μM SANGER
human SW1710 cell Growth inhibition assay Inhibition of human SW1710 cell growth in a cell viability assay, IC50=1.62628 μM SANGER
human EW-13 cell Growth inhibition assay Inhibition of human EW-13 cell growth in a cell viability assay, IC50=1.63466 μM SANGER
human U251 cell Growth inhibition assay Inhibition of human U251 cell growth in a cell viability assay, IC50=1.74031 μM SANGER
human NCI-H460 cell Growth inhibition assay Inhibition of human NCI-H460 cell growth in a cell viability assay, IC50=2.04839 μM SANGER
human DU-4475 cell Growth inhibition assay Inhibition of human DU-4475 cell growth in a cell viability assay, IC50=2.14759 μM SANGER
human MFE-296 cell Growth inhibition assay Inhibition of human MFE-296 cell growth in a cell viability assay, IC50=2.47792 μM SANGER
human DU-145 cell Growth inhibition assay Inhibition of human DU-145 cell growth in a cell viability assay, IC50=2.49118 μM SANGER
human MDA-MB-231 cell Growth inhibition assay Inhibition of human MDA-MB-231 cell growth in a cell viability assay, IC50=2.49572 μM SANGER
human SNU-387 cell Growth inhibition assay Inhibition of human SNU-387 cell growth in a cell viability assay, IC50=2.5282 μM SANGER
Click to View More Cell Line Experimental Data

Biological Activity

Description 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.
Targets
FAK [1]
(Cell-free assay)		 PYK2 [1]
(Cell-free assay)		 CDK2/CyclinE [1]
(Cell-free assay)		 CDK3/CyclinE [1]
(Cell-free assay)		 CDK1/CyclinB [1]
(Cell-free assay)		 Click to View More Targets
1.5 nM 13 nM 30 nM 47 nM 58 nM
In vitro
In vitro PF-562271 Besylate 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 μM, 2.08 μM and 2.01 μM, respectively. [2]
Kinase Assay Recombinant kinase assay and enzyme kinetics
Briefly, purified-activated FAK kinase domain (amino acid 410–689) is reacted with 50 μM ATP and 10 μg 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 μM. 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.
Cell Research Cell lines Squamous cell carcinoma (SCC)
Concentrations 0 to 1 μM
Incubation Time 72 hours
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.
In Vivo
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]
Animal Research Animal Models PC-3M, BT474, BxPc3, LoVo, U87MG, H125 and H460 cells are injected s.c. into the right flank of athymic female mice .
Dosages ≤100 mg/kg
Administration Administered via p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00666926 Completed
Head and Neck Neoplasm|Prostatic Neoplasm|Pancreatic Neoplasm
Verastem Inc.
 December 2005 Phase 1

Chemical Information & Solubility

Molecular Weight 665.66 Formula

C21H20F3N7O3S.C6H6O3S
CAS No. 939791-38-5 SDF Download PF-562271 Besylate SDF
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
Storage (From the date of receipt)

In vitro
Batch:

4-Methylpyridine : 25 mg/mL

DMSO : 0.4 mg/mL ( (0.6 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble


Molecular Weight Calculator

In vivo
Batch:

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In vivo Formulation Calculator

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In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
We are planning both in vitro and in vivo experiments and want to know how to reconstitute the drug for these purposes?

Answer:
PF-00562271 has poor solubility in DMSO and water. Its solubility in DMSO is only 0.4mg/ml. In a previous literature report (http://www.ncbi.nlm.nih.gov/pubmed/18339875), the author used 5% Gelucire to formulate the compound. You can also consider other co-solvents such as PEG400, CMC, Tween80, and Captisol.

Question 2:
Can you provide with a few common vehicles for PF-00562271, S2672 for use as oral gavage?

Answer:
S2672 PF-00562271 can be dissolved in 0.5% CMC Na at 30 mg/ml as a suspension. If 4% DMSO can be used in your experiment, it will help dissolving the suspension more homogeneously.

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