PF-00562271

PF-00562271は、焦点粘着力キナーゼ(FAK)とPyk2触媒活性の強力な、ATP競争的、可逆的な阻害剤で、IC50 がそれぞれ 1.5 nM と 14 nMです。

目録号S2672
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PF-00562271 化学構造
分子量: 665.66

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製品情報

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製品の説明

生物活性

情報 PF-00562271は、焦点粘着力キナーゼ(FAK)とPyk2触媒活性の強力な、ATP競争的、可逆的な阻害剤で、IC50 がそれぞれ 1.5 nM と 14 nMです。
目標 FAK Pyk2
IC50 1.5 nM 14 nM [1]
In vitro試験 PF-562271 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試験 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]
臨床試験
特集

推薦された実験操作 (公開の文献だけ)

キナーゼアッセイ: [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.

細胞アッセイ: [2]

細胞系 Squamous cell carcinoma (SCC)
濃度 0 to 1 μM
処理時間 72 hours
方法 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: [1]

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 .
製剤 PF-562271 is dissolved in 5% Gelucire.
投薬量 ≤100 mg/kg
管理 Administered via p.o.
1

参考

化学情報

Download PF-00562271 SDF
分子量 665.66
化学式

C21H20F3N7O3S.C6H6O3S

CAS No. 939791-38-5
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 14 mg/mL heat (21 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
* <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.
化学名 N-methyl-N-(3-((2-(2-oxoindolin-5-ylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)methanesulfonamide benzenesulfonate

研究分野

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Source , , Mol Ther, 2012, 20(5):972-83. PF-00562271 purchased from Selleck
Method rAAV-luciferase transduction assay
Cell Lines Fibroblasts and HeLa cells
Concentrations 1 uM
Incubation Time 24 h
Results Pharmacologic inhibition of FAK kinase activity with PF-00562271 blocked Mn <SUP>++</SUP> -induced transduction, confirming that the effect of Mn <SUP>++</SUP> requires FAK kinase activity.

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技術サポート&よくある質問(FAQ)

顧客がするかもしれない質問に対する答えは、指示を取り扱っている阻害剤で見つかります。話題は、貯蔵液(阻害剤と特別な注意を細胞ベースの分析法と動物のために必要とする問題を保存することは実験します)を準備する方法を含みます。

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