| 名称 | PF-562271 |
| 描述 | PF-562271 is an effective ATP-competitive, reversible inhibitor of FAK(IC50=1.5 nM) and Pyk2 kinase(IC50=13 nM). |
| 细胞实验 | PF-562271 (Haoyuan Chemexpress Co., Ltd.) is dissolved in DMSO and stored, and then diluted with appropriate media before use[2]. Ewing sarcoma cells are plated in 10-cm dishes, allowed to adhere for 24 hours, and then treated with PF-562271, PD0325901, or Dasatinib. ATP content is measured as a surrogate for cell number using the CellTiter-Glo Luminescent Cell Viability Assay. Luminescence readings are obtained using the FLUOstar Omega microplate reader. For experiments with small-molecule treatment, 1.25×103 Ewing sarcoma cells are seeded in each well and treated with a range of concentrations. IC50 values are calculated from ATP measurements obtained after 3 days of treatment using log-transformed, normalized data in GraphPad Prism 5.0. Cell lines are also treated with compound in 6-cm dishes, trypsinized, and counted by light microscopy using trypan blue exclusion. For experiments using shRNA-transduced cells, 1.25×103 cells are seeded per well into 384-well plates on day 3 posttransduction. ATP content is measured on days 3, 6, and 8 posttransduction[2]. |
| 激酶实验 | The 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 min. Phosphorylation of p(Glu/Tyr) is challenged with serially diluted compound 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[1]. |
| 体外活性 | 在胫骨植入MDA-MB-231细胞的大鼠中,口服 PF-562271（5 mg/kg）,引起骨钙素和松质骨增加,从而使肿瘤细胞生长减缓.在携带H125肺部异种移植肿瘤、异种移植PC3M-luc-C6的小鼠模型中,口服 PF-562271 （25 mg/kg）抑制肿瘤细胞生长,引起细胞凋亡.在U87 mg的小鼠中,PF-562271（口服< 33 mg/kg）能够以时间和剂量依赖的方式抑制肿瘤中FAK磷酸化.在BxPc3异种移植小鼠、PC3-M异种移植小鼠中口服 PF-562271（50 mg/kg）,能够抑制肿瘤生长. |
| 体内活性 | PF-562271能够结合在ATP与FAK结合的部位,并在激酶铰链区形成抑制剂与主链原子之间的氢键。在鸡胚绒毛尿囊膜中,PF-562271（1 nM ）阻断bFGF刺激的血管生成。在PC3-M细胞中,PF-562271（3.3 μM）能够使细胞停止在G1期。对于A431 细胞,PF-562271（250 nM ）能够抑制细胞侵入胶原蛋白。 |
| 存储条件 | Store at low temperature
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 235 mg/mL (463.06 mM), Sonication is recommended.
10% DMSO+90% Saline : < 10 mg/mL (19.7 mM), Lower concentrations may be soluble, but exact solubility limit is unknown.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 10 mg/mL (19.7 mM), Solution.
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| 关键字 | VS-6062 | VS6062 | VS 6062 | Sarcoma | Pyk2 | PTK2 protein tyrosine kinase 2 | PTK2 | Proline-rich tyrosine kinase 2 | PF-562271 | Inhibitor | inhibit | Focal adhesion kinase | FAK | Ewing | CDK3/CyclinE | CDK2/CyclinE | CDK1/CyclinB | Cancer | Breast | Antitumor |
| 相关产品 | 2,4,6-Trihydroxybenzoic acid | Seliciclib | Ifebemtinib | 2-Chloropyrazine | Sodium Oxamate | Abemaciclib methanesulfonate | Ribociclib | Abemaciclib | Amantadine | (E)-β-Farnesene | Dinaciclib | Kojic acid |
| 相关库 | 抑制剂库 | 抗癌活性化合物库 | 经典已知活性库 | 已知活性化合物库 | 激酶抑制剂库 | 含氟化合物库 | 抗衰老化合物库 | 膜蛋白靶向化合物库 | 酪氨酸激酶分子库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |