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Synonyms | PF-00562271 Besylate | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C21H20F3N7O3S.C6H6O3S |
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分子量 | 665.66 | CAS No. | 939791-38-5 | |
Solubility (25°C)* | 体外 | 4-Methylpyridine | 25 mg/mL (37.55 mM) | |
DMSO | 0.4 mg/mL warmed with 50ºC water bath (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. |
製品説明 | 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. |
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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] |
キナーゼアッセイ | Recombinant kinase assay and enzyme kinetics | |
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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. | ||
細胞アッセイ | 細胞株 | Squamous cell carcinoma (SCC) |
濃度 | 0 to 1 μM | |
反応時間 | 72 hours | |
実験の流れ | 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. |
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動物実験 | 動物モデル | PC-3M, BT474, BxPc3, LoVo, U87MG, H125 and H460 cells are injected s.c. into the right flank of athymic female mice . |
投薬量 | ≤100 mg/kg | |
投与方法 | Administered via p.o. |
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]
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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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