PF-562271-besylate-PF562271-besylate-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPF-562271 besylateCat. No.: HY-10458CAS No.: 939791-38-5Synonyms: PF562271 besylate; PF 562271 besylate分式: CHFNOS分量: 665.66作靶點: FAK; Pyk2作通路: Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-

2、20C 1 month溶解性數據體外實驗 DMSO : 21.4 mg/mL (32.15 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.5023 mL 7.5113 mL 15.0227 mL5 mM 0.3005 mL 1.5023 mL 3.0045 mL10 mM 0.1502 mL 0.7511 mL 1.5023 mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案，配制

3、前請先配制澄的儲備液，再依次添加助溶劑(為保證實驗結果的可靠性，體內實驗的作液，建議您現現配，當天使；澄的儲備液可以根據儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 1.67 mg/mL (2.51 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.67 mg/mL (2.51 mM); Clear solution3.

4、 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 1.67 mg/mL (2.51 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 PF-562271 besylate有效，可逆，ATP競爭性的 FAK 和 Pyk2 激酶抑制劑，IC50 分別為 1.5 和 13 nM 1。IC50 & Target IC50: 1.5 nM (FAK), 13 nM (Pyk2), 30 nM (CDK2), 47 nM (CDK3),

5、 58 nM (CDK1), 97 nM (CDK7), 97 nM(Flt3) 1體外研究 PF-562,271 is a 30- to 120-nM (15.2 to 60.1 ng/mL) inhibitor of cdk2/E, cdk5/p35, cdk1/B, and cdk3/E inrecombinant enzyme assays 1. PF-562,271 blocks bFGF-stimulated blood vessel angiogenesis asperformed in chicken chorioallantoic membrane assays 2. Tre

6、atment of cells with PF-562,271 or knock-down of FAK by siRNA is observed to increase cell-cell adhesion strength 3.體內研究 PF-562,271 (33 mg/kg, p.o.) inhibits FAK phosphorylation in tumors in a dose- and time-dependent mannerin tumor-bearing mice. FAK phosphorylation inhibition relative to total bloo

7、d concentration of PF-562,271results in a calculated EC50 of 93 ng/mL. PF-562,271 (25 mg/kg, p.o.) induces apoptosis 2-fold greater intreated tumors compared with vehicle-treated control tumors on day 3 1. PF-562,271 (33 mg/kg, p.o.) anddasatinib extensively inhibit the movement of tumor cells in th

8、e animals. Inhibition of FAK kinase activityfollowing treatment with PF-562,271 results in altered E-cadherin dynamics in vivo 3.PROTOCOLKinase Assay 1 Briefly, purified-activated FAK kinase domain (amino acid 410-689) is reacted with 50 M ATP and 10 g perwell of a random peptide polymer of Glu and

9、Tyr, p(Glu/Tyr), in kinase buffer 50 mM HEPES (pH 7.5), 125mM NaCl, and 48 mM MgCl2 for 15 min. Phosphorylation of p(Glu/Tyr) is challenged with serially dilutedcompound at 1/2-Log concentrations starting at a top concentration of 1 M. Each concentration is tested intriplicate. Phosphorylation of p(

10、Glu/Tyr) is detected with a general antiphospho-tyrosine (PY20) antibodyfollowed by horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG antibody. HRP substrate isadded, and absorbance readings at 450 nm are obtained after addition of stop solution (2mol/LH2SO4). IC50values are determined usi

11、ng the Hill-Slope Model.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Exponentially growing cells are trypsinized and resuspended in sterile PBS and inoculated s.c. (1106 cellsAdministration 1 per mouse in 200 L) into the right flank of mice. A

12、nimals bearing tumors of appr 150 mm3 in size are dividedinto groups receiving either vehicle (5% Gelucire) or PF-562,271 (diluted in vehicle), and dosed by p.o.gavage. Animal body weight and tumor measurements are obtained every 2 d. Tumor volume (mm3) ismeasured with Vernier calipers and calculate

13、d. For all tumor growth inhibition experiments, 8 to 10 mice perdose group are used.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發(fā)表的科研獻2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Clin Can

14、cer Res. 2019 Jul 15;25(14):4552-4566. Cancer Res. 2013 May 1;73(9):2873-83. Int J Cancer. 2015 Oct 1;137(7):1549-59. Sci Rep. 2018 May 8;8(1):7228.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Roberts WG, et al. Antitumor activity and pharmacology of a selective focal adhesi

15、on kinase inhibitor, PF-562,271. Cancer Res, 2008,68(6), 1935-1944.2. Lim ST, et al. FERM control of FAK function: implications for cancer therapy. Cell Cycle, 2008, 7(15), 2306-2314.3. Canel M, et al. Quantitative in vivo imaging of the effects of inhibiting integrin signaling via Src and FAK on cancer cell movement:effects on E-cadherin dynamics. Cancer Re