ホームページ Angiogenesis FAK inhibitor - Pyk2 inhibitor - CDK inhibitor PF-562271 Besylate For research use only.

PF-562271 Besylate

別名：PF-00562271 Besylate

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化学構造

CAS No. 939791-38-5

サイズ 価格(税別) 在庫状況
JPY 25500 国内在庫あり
JPY 40500 国内在庫あり
JPY 122500 国内在庫あり
JPY 598500 国内在庫なし(納期7~10日)

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PF-562271 Besylate関連製品

シグナル伝達経路

FAK Signaling Pathways

FAKシグナル伝達経路

FAK阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
human SNU-387 cell Growth inhibition assay Inhibition of human SNU-387 cell growth in a cell viability assay, IC50=2.5282 μM SANGER
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 SANGER
human DU-145 cell Growth inhibition assay Inhibition of human DU-145 cell growth in a cell viability assay, IC50=2.49118 μM SANGER
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生物活性

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.
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)		 もっとクリックする
1.5 nM 13 nM 30 nM 47 nM 58 nM
In Vitro
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]
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.
細胞実験 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.
In Vivo
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]
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 .
投与量 ≤100 mg/kg
投与経路 Administered via p.o.
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

化学情報

分子量 665.66 化学式

C21H20F3N7O3S.C6H6O3S
CAS No. 939791-38-5 SDF Download PF-562271 Besylate SDFをダウンロードする
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
保管

In vitro
Batch:

4-Methylpyridine : 25 mg/mL

DMSO : 0.4 mg/mL ( (0.6 mM)； 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機
Clear solution
4%DMSO 30% 66%ddH2O
3.0mg/ml (4.51mM) Taking the 1 mL working solution as an example, add 40 μL of 75 mg/ml clarified DMSO stock solution to 300 μL of PEG 300, mix evenly to clarify it; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

mg/kg g μL 匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH2O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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よくある質問（FAQ）

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

回答
PF-00562271 has poor solubility in DMSO and water. Its solubility in DMSO is only 0.4mg/ml. In a previous literature report (http://www.ncbi.nlm.nih.gov/pubmed/18339875), the author used 5% Gelucire to formulate the compound. You can also consider other co-solvents such as PEG400, CMC, Tween80, and Captisol.

質問2:
Can you provide with a few common vehicles for PF-00562271, S2672 for use as oral gavage?

回答
S2672 PF-00562271 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.

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