Powder: -20°C for 3 years | In solvent: -80°C for 1 year
PF04217903 是一种高效的、 ATP 竞争性的c-Met 激酶抑制剂(Ki=4.8 nM),相对于 208 个激酶,PF04217903 显示出 1000 倍以上的选择性。它抗血管生成作用。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 233 | 现货 | ||
2 mg | ¥ 329 | 现货 | ||
5 mg | ¥ 538 | 现货 | ||
10 mg | ¥ 868 | 现货 | ||
25 mg | ¥ 1,490 | 现货 | ||
50 mg | ¥ 2,230 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 596 | 现货 |
产品描述 | MET Tyrosine Kinase Inhibitor PF-04217903 is an orally bioavailabe, small-molecule tyrosine kinase inhibitor with potential antineoplastic activity. |
靶点活性 | c-Met:4.8 nM |
体外活性 | 尽管在舒尼替尼敏感的B16F1和Tib6肿瘤模型中不能抑制肿瘤生长,但与单独使用舒尼替尼或PF-04217903相比,PF-04217903和舒尼替尼联用显著抑制舒尼替尼耐受性EL4和LLC肿瘤模型的肿瘤生长,血管扩张,表明舒尼替尼耐药肿瘤中HGF/c-Met轴的功能作用. |
体内活性 | PF-04217903明显抑制 LXFA 526L和LXFA 1647L克隆生长,IC50分别为16 nM和13 nM,与西妥昔单抗联用效果增强。PF-04217903有效抑制c-Met驱动的生物过程,如多种肿瘤细胞的生长,运动,侵袭和形态学变化。2 μM PF-04217903促进GTL-16 细胞死亡,其涉及磷酸化的4E-BP1,ERK/MAPK相关蛋白和 PI3K/AKT通路的下调。PF-04217903选择性比十字孢碱或PF-02341066高,PF-04217903作用于c-Met选择性比作用于其他一组208种激酶选择性高1000多倍,对c-Met致癌突变更敏感。除WT c-Met之外,PF-04217903显示出类似的抑制c-Met-H1094R,c-Met-R988C和c-Met-T1010I活性的效力,IC50为3.1 nM,6.4 nM和6.7 nM,但对c-Met-Y1230C没有抑制活性,IC50>10 μM。PF-04217903和舒尼替尼联用明显抑制内皮细胞增殖,但是不抑制肿瘤细胞B16F1,Tib6,EL4和LLC。 |
激酶实验 | Cellular c-Met phosphorylation ELISA: A549 cells with endogenous human WT c-Met are seeded in 96-well plates in growth medium and cultured overnight. On the second day of the assay, the growth medium is replaced with serum-free medium (with 0.04% BSA). Serial dilutions of PF-04217903 are added to each well, and cells are incubated at 37 °C for 1 hour. Then 40 ng/mL HGF is added to the cells for 20 minutes. The cells are washed once with HBSS supplemented with 1 mM Na3VO4, and protein lysates are generated from cells using lysis buffer. Phosphorylation of c-Met is assessed by an ELISA method utilizing capture antibodies specific for c-Met and a detection antibody specific for phosphorylated tyrosine residues. Antibody-coated plates are incubated in the presence of protein lysates at 4 °C overnight and washed with 1% Tween 20 in PBS seven times. HRP-PY20 (horseradish peroxidase-conjugated anti-phosphotyrosine) is diluted 1:500 in blocking buffer and added to each plate for 30 minutes. Plates are then washed again, and TMB peroxidase substrate is added to initiate the HRP-dependent colorimetric reaction and the reaction stopped by addition of 0.09 N H2SO4. ELISA end points are the absorbance measured at 450 nm using a spectrophotometer. IC50 value is calculated by concentration-response curve fitting utilizing a Microsoft Excel-based four-parameter analytical met |
细胞实验 | Cells are treated with different concentrations PF-04217903 for 4 days. Cell proliferation is assessed by counting content of each well using a Coulter counter machine.(Only for Reference) |
分子量 | 372.38 |
分子式 | C19H16N8O |
CAS No. | 956905-27-4 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 5 mg/mL (13.42 mM)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.6854 mL | 13.4271 mL | 26.8543 mL | 67.1357 mL |
5 mM | 0.5371 mL | 2.6854 mL | 5.3709 mL | 13.4271 mL | |
10 mM | 0.2685 mL | 1.3427 mL | 2.6854 mL | 6.7136 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
PF-04217903 956905-27-4 Tyrosine Kinase/Adaptors c-Met/HGFR lung migration gastric GTL-16 inhibit phosphorylation colon PF 04217903 phospho-PDGFRβ PF04217903 carcinoma Inhibitor inhibitor