| 名稱 | 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. |
| 細(xì)胞實(shí)驗(yàn) | 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) |
| 激酶實(shí)驗(yàn) | 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. |
| 體外活性 | 在風(fēng)濕性關(guān)節(jié)炎模型中,Fostamatinib 明顯減少炎癥介質(zhì),比如TNFalpha,IL-1,IL-6和IL-18,從而減少炎癥和骨退化.Fostamatinib 能夠有效抑制體內(nèi)BCR信號,導(dǎo)致惡性B細(xì)胞的增殖和存活減少,并明顯延長治療組動(dòng)物的存活.在逆轉(zhuǎn)-被動(dòng)阿瑟斯反應(yīng)和雙抗體誘導(dǎo)的關(guān)節(jié)炎小鼠模型中,口服Fostamatinib減少免疫復(fù)合物介導(dǎo)的炎癥. |
| 體內(nèi)活性 | 在人肥大細(xì)胞,巨噬細(xì)胞,和中性粒細(xì)胞中,Fostamatinib能夠特異性抑制FcγR信號。在大部分DLBCL細(xì)胞系,Fostamatinib誘導(dǎo)細(xì)胞凋亡。Fostamatinib（EC50 =56 nM）以劑量依賴方式抑制抗- IgE介導(dǎo)的CHMC脫粒,它也會(huì)抑制抗-IgE誘導(dǎo)的LTC4,細(xì)胞因子以及趨化因子,包括TNFα,IL-8,和GM-CSF的產(chǎn)生與釋放。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 107 mg/mL (184.3 mM)
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| 關(guān)鍵字 | Inhibitor | Spleen tyrosine kinase | Cluster of differentiation antigen 135 | Fms like tyrosine kinase 3 | CD135 | inhibit | Fostamatinib | FLT3 | Syk | R 788 | R-788 |
| 相關(guān)產(chǎn)品 | Adenosine 5'-monophosphate monohydrate | Inosine | Gilteritinib | ANTHRAQUINONE-2-CARBOXYLIC ACID | Theophylline | Acefylline | Theobromine | Nintedanib | Sorafenib | Theophylline monohydrate | Diphylline | Doxofylline |
| 相關(guān)庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 抗病毒庫 | FDA 上市藥物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 |