Name: PF-562271 Besylate
Brand: Selleck Chemicals
SKU: S2672
Rating: 5 (26 reviews)

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

CAS: 939791-38-5

Selleck's PF-562271 Besylate has been cited by 26 Publications

4 Customer Reviews

Purity & Quality Control

Batch: Purity: 99.32%

99.32

PF-562271 Besylate Related Products

Related Compound Libraries	Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Angiogenesis Related compound Library HIF-1 Signaling Pathway Compound Library FDA-approved Anticancer Drug Library	Click to Expand

Signaling Pathway

FAK Signaling Pathway

Choose Selective FAK Inhibitors

Cell Data

Cell Lines	Assay Type	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	Click to View More Targets

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
Kinase Assay	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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT00666926	Completed	Head and Neck Neoplasm\|Prostatic Neoplasm\|Pancreatic Neoplasm	Verastem Inc.	December 2005	Phase 1

References

[4] Bagi CM, et al. Cancer Biol Ther. 2009, 8(9), 856-865.

+ Expand

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)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

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:

Add solvents to the product individually and in order.

In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

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.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):