Home Angiogenesis FAK inhibitor PF-562271 Besylate

research use only

PF-562271 Besylate FAK inhibitor

Cat.No.S2672

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 FAK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 665.66

Jump to

Quality Control

Batch: Purity: 99.32%
99.32

Cell Culture, Treatment & Working Concentration

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

Solubility

In vitro
Batch:

4-Methylpyridine : 25 mg/mL

DMSO : 0.4 mg/mL (0.6 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight
Dilution Calculator Molecular Weight Calculator

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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

mg/kg
g
μL

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.

Chemical Information, Storage & Stability

Molecular Weight 665.66 Formula

C21H20F3N7O3S.C6H6O3S

 Storage (From the date of receipt)
CAS No. 939791-38-5 Download SDF Storage of Stock Solutions

Synonyms PF-00562271 Besylate 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

Mechanism of Action

Targets/IC50/Ki
FAK
(Cell-free assay)
1.5 nM
PYK2
(Cell-free assay)
13 nM
CDK2/CyclinE
(Cell-free assay)
30 nM
CDK3/CyclinE
(Cell-free assay)
47 nM
CDK1/CyclinB
(Cell-free assay)
58 nM
CDK7/CyclinH/MAT1
(Cell-free assay)
97 nM
FLT3
(Cell-free assay)
97 nM
GSK-3α
(Cell-free assay)
101 nM
CDK5/p35
(Cell-free assay)
120 nM
GSK-3β
(Cell-free assay)
133 nM
Aurora A
(Cell-free assay)
145 nM
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. 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
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.
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.
References
  • [4] https://pubmed.ncbi.nlm.nih.gov/19458500/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

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

Answer:
It has poor solubility in DMSO and water, with solubility in DMSO being only 0.4mg/ml. In a previous literature report (http://www.ncbi.nlm.nih.gov/pubmed/18339875), the author used 5% Gelucire to formulate this 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 it, S2672 for use as oral gavage?

Answer:
It 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.

Signaling Pathway Map