PF-562271 Besylate

製品コードS2672 バッチS267201

印刷

化学情報

Chemical Structure Synonyms PF-00562271 Besylate Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C21H20F3N7O3S.C6H6O3S
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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 PF-562271 BesylateはPF-562271のベンゼンスルホン酸塩で、これは強力なATP競合性可逆的FAK阻害剤であり、IC50は1.5 nMです。Pyk2に対してはFAKよりも約10分の1の効力しかなく、一部のCDKを除いて他のProtein Tyrosine Kinaseに対しては100倍以上の選択性を示します。フェーズ1。
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.
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.

プロトコル(参考用のみ)

キナーゼアッセイ 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.
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.
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.

参考

  • https://pubmed.ncbi.nlm.nih.gov/18339875/
  • https://pubmed.ncbi.nlm.nih.gov/21823119/
  • https://pubmed.ncbi.nlm.nih.gov/20495381/
  • https://pubmed.ncbi.nlm.nih.gov/19458500/

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Glycoprotein NMB mediates bidirectional GSC-TAM interactions to promote tumor progression [ JCI Insight, 2025, 10(13)e187684] PubMed: 40626360
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

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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