| 名称 | Fostamatinib |
| 描述 | Fostamatinib (R788)(IC50 of 41 nM), which is a prodrug of the active metabolite R406, is a Syk inhibitor. It does not work on Lyn. |
| 细胞实验 | Cultured human mast cells (CHMC) are derived from cord blood CD34+ progenitor cells and grown, primed, and stimulated and shown in supplemental data. Before stimulation, cells are incubated with R788 or DMSO for 30 minutes. Cells are then stimulated with either 0.25 to 2 mg/mL anti-IgE or anti-IgG or 2 μM ionomycin. For tryptase measurement, ∼1500 cells per well are stimulated for 30 min in modified Tyrode's buffer. For LTC4 and cytokine production, 100,000 cells per well are stimulated for 1 or 7 hours, respectively. Tryptase activity is measured by luminescence readout of a peptide substrate, and LTC4 and cytokines are measured using Luminex multiplex technology. (Only for Reference) |
| 激酶实验 | Fluorescence polarization kinase assay and Ki determination: The fluorescence polarization reactions are performed. For Ki determination, duplicate 200-μL reactions are set up at eight different ATP concentrations from 200 μM (2-fold serial dilutions) in the presence of either DMSO or R788 at 125, 62.5, 31.25, 15.5, or 7.8 nM. At different time points, 20 μL of each reaction is removed and quenched to stop the reaction. For each concentration of R788, the rate of reaction at each concentration of ATP is determined and plotted against the ATP concentration to determine the apparent Km and Vmax (maximal rate). Finally the apparent Km (or apparent Ki/Vmax) is plotted against the inhibitor concentration to determine the Ki. |
| 体外活性 | 在风湿性关节炎模型中,Fostamatinib 明显减少炎症介质,比如TNFalpha,IL-1,IL-6和IL-18,从而减少炎症和骨退化.Fostamatinib 能够有效抑制体内BCR信号,导致恶性B细胞的增殖和存活减少,并明显延长治疗组动物的存活.在逆转-被动阿瑟斯反应和双抗体诱导的关节炎小鼠模型中,口服Fostamatinib减少免疫复合物介导的炎症. |
| 体内活性 | 在人肥大细胞,巨噬细胞,和中性粒细胞中,Fostamatinib能够特异性抑制FcγR信号。在大部分DLBCL细胞系,Fostamatinib诱导细胞凋亡。Fostamatinib（EC50 =56 nM）以剂量依赖方式抑制抗- IgE介导的CHMC脱粒,它也会抑制抗-IgE诱导的LTC4,细胞因子以及趋化因子,包括TNFα,IL-8,和GM-CSF的产生与释放。 |
| 存储条件 | store at low temperature,keep away from moisture | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 127.5 mg/mL (219.65 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 4 mg/mL (6.89 mM), Sonication is recommended.
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| 关键字 | Syk | Spleen tyrosine kinase | R-788 | R 788 | MonoamineTransporter | Monoamine Transporter | Monoamine transporter | Inhibitor | inhibit | Fostamatinib | Fms like tyrosine kinase 3 | FLT3 | Cluster of differentiation antigen 135 | CD135 | AdenosineReceptor | Adenosine transporter | Adenosine Receptor | A3 |
| 相关产品 | Inosine | Gilteritinib | ANTHRAQUINONE-2-CARBOXYLIC ACID | Theophylline | Adenosine 5'-monophosphate disodium salt | Acefylline | Theobromine | Sorafenib | Theophylline monohydrate | Adenosine monophosphate | Sulcatone | Doxofylline |
| 相关库 | 抑制剂库 | 抗癌上市药物库 | 已知活性化合物库 | EMA 上市药物库 | FDA 上市药物库 | 抗病毒库 | GPCR靶点分子库 | 膜蛋白靶向化合物库 | 药物功能重定位化合物库 | FDA 上市激酶抑制剂库 | 酪氨酸激酶分子库 | 抗癌临床化合物库 |