| 名称 | PF-04217903 |
| 描述 | MET Tyrosine Kinase Inhibitor PF-04217903 is an orally bioavailabe, small-molecule tyrosine kinase inhibitor with potential antineoplastic activity. |
| 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) |
| 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 |
| 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。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 20 mg/mL (53.71 mM), Sonication is recommended.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 关键字 | lung | migration | gastric | GTL-16 | PF-04217903 | c-Met/HGFR | inhibit | phosphorylation | colon | PF 04217903 | phospho-PDGFRβ | PF04217903 | carcinoma | Inhibitor |
| 相关产品 | Capmatinib 2HCl | Cabozantinib S-malate | Crizotinib | Amuvatinib | BMS 777607 | (±)-Norcantharidin | Capmatinib xHCl | LMTK3-IN-1 | L-Ascorbic acid 2-phosphate trisodium | Norcantharidin | Bacitracin Zinc | AMG-458 |
| 相关库 | 抑制剂库 | 经典已知活性库 | 抗癌活性化合物库 | 已知活性化合物库 | 激酶抑制剂库 | 高选择性抑制剂库 | 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 |