PF-562271 Besylate

Catalog No.S2672 Batch:S267201

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Technical Data

Formula

C21H20F3N7O3S.C6H6O3S
Molecular Weight 665.66 CAS No. 939791-38-5
Solubility (25°C)* In vitro 4-Methylpyridine 25 mg/mL (37.55 mM)
DMSO 0.4 mg/mL (0.6 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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)		 View More
1.5 nM 13 nM 30 nM 47 nM 58 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. [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]
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]

Protocol (from reference)

Kinase Assay:

[1]
  • 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 Assay:

[2]
  • 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.
Animal Study:

[1]
  • 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.

Customer Product Validation

Data from [Mol Ther, 2012, 20(5), 972-83]

Data from [Data independently produced by , , Cell Signal, 2018, 42:176-183]

Data from [Data independently produced by , , J Cancer, 2018, 9(19):3603-3612]

Data from [Data independently produced by , , BMB Rep, 2015, 48(11):630-5]

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

The PMA phorbol ester tumor promoter increases canonical Wnt signaling via macropinocytosis [ Elife, 2023, 12RP89141] PubMed: 37902809
The PMA Phorbol Ester Tumor Promoter Increases Canonical Wnt Signaling Via Macropinocytosis [ bioRxiv, 2023, 2023.06.02.543509] PubMed: 37333286
Pharmacological Inhibition of FAK-Pyk2 Pathway Protects Against Organ Damage and Prolongs the Survival of Septic Mice [ Front Immunol, 2022, 13:837180] PubMed: 35178052
pncCCND1_B Engages an Inhibitory Protein Network to Downregulate CCND1 Expression upon DNA Damage [ Cancers (Basel), 2022, 14(6)1537] PubMed: 35326688
A Systems Biology Approach to Investigate Kinase Signal Transduction Networks That Are Involved in Triple Negative Breast Cancer Resistance to Cisplatin [ J Pers Med, 2022, 12-81277] PubMed: 36013226
FNDC5/irisin facilitates muscle-adipose-bone connectivity through ubiquitination-dependent activation of runt-related transcriptional factors RUNX1/2 [ J Biol Chem, 2022, S0021-9258(22)00119-3] PubMed: 35124008
Milk fat globule EGF factor 8 restores mitochondrial function via integrin-medicated activation of the FAK-STAT3 signaling pathway in acute pancreatitis [ Clin Transl Med, 2021, 11(2):e295] PubMed: 33634976
Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy [ J Nanobiotechnology, 2021, 19(1):175] PubMed: 34112200
Synthesis and evaluation of FAK inhibitors with a 5-fluoro-7H-pyrrolo[2,3-d]pyrimidine scaffold as anti-hepatocellular carcinoma agents [ Eur J Med Chem, 2021, 223:113670] PubMed: 34214842
Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing [ Cells, 2021, 10(3)663] PubMed: 33809739

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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