| 名称 | Fostamatinib |
| 描述 | Fostamatinib (R788) is a small-molecule inhibitor and an oral prodrug of R406, a Syk/FLT3-targeted inhibitor (IC50 = 41 nM) that also inhibits Lyn (IC50 = 63 nM) and Lck (IC50 = 37 nM), featuring oral activity and cell permeability, used for the treatment of immune thrombocytopenia. |
| 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 | 方法：在体外实验中，从健康对照者分离的单核细胞与R406（fostamatinib活性代谢物，2 µM）共孵育24小时，进行红细胞吞噬及TNF-α产生测定。
结果：R406显著降低单核细胞对IgG包被红细胞的吞噬（58.8%降至5.6%），并强烈抑制血红素或AIHA患者红细胞诱导的TNF-α产生。[1]
方法：采用HK、K30、TE1细胞，以10 μM Fostamatinib处理24-48 h，通过CCK-8、Transwell、划痕实验及Western blot检测。
结果： Fostamatinib显著抑制细胞增殖、侵袭、迁移及LYN蛋白表达。[2] |
| 体内活性 | 方法：在Louvain大鼠中单次口服给予Fostamatinib (R788) 10 mg/kg或20 mg/kg，检测其活性代谢物R406的血药浓度，计算药代动力学参数包括AUC0-16 hrs、Cmax和半衰期，并监测血浆中前药的存在情况。
结果：R406在10 mg/kg和20 mg/kg剂量下的AUC0-16 hrs分别为10618 ng·h/mL和30650 ng·h/mL，Cmax分别为2600 ng/mL和6500 ng/mL（均在给药后1小时达到），半衰期均为4.2小时；血浆中未检测到前药R788，表明其完全转化为R406。[3] |
| 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 | 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 | Acefylline | Theobromine | Sorafenib | Pexidartinib | Theophylline monohydrate | Adenosine monophosphate | Sulcatone | Doxofylline |
| 相关库 | 抗癌上市药物库 | 已知活性化合物库 | EMA 上市药物库 | 激酶抑制剂库 | 抗病毒库 | FDA 上市药物库 | GPCR靶点分子库 | 膜蛋白靶向化合物库 | 免疫/炎症分子化合物库 | FDA 上市激酶抑制剂库 | 药物功能重定位化合物库 | 抗癌临床化合物库 |