Fostamatinib (R788) 是活性化合物 R406 的口服前藥，R406 是一種相對(duì)選擇性的 Syk 小分子抑制劑[1]。 R406 是 ATP 結(jié)合 Syk 催化結(jié)構(gòu)域 (Ki = 30 nM) 的競(jìng)爭(zhēng)性抑制劑，在體外抑制 Syk 激酶活性，IC50 為 41 nM [2]。

Fostamatinib (R788) 誘導(dǎo) Waldenstr?m 巨球蛋白血癥 (WM) MWCL-1 和 BWCM.1 細(xì)胞的存活時(shí)間和劑量依賴性降低，IC50 分別在大約 0.25 和 1 μM 的生理相關(guān)范圍內(nèi)，第 3 天 [3]。 Fostamatinib (R788) 在體外顯著抑制了 6 種 HPV 陰性 HNSCC 細(xì)胞系的增殖[4]。

Fostamatinib (R788)（80 mg/kg/d，21 天）顯著延長(zhǎng)了受到白血病細(xì)胞系 TCL1-551 和 TCL1-870 攻擊的小鼠的存活時(shí)間 [5]。 Fostamatinib (R788)（80 mg/kg/d，7 天）在非霍奇金淋巴瘤 (NHL) 小鼠模型中顯示出療效，可減輕治療小鼠的腫瘤負(fù)荷并延長(zhǎng)生存期[6] .單次口服 R788 10 mg/kg 或 20 mg/kg:Louvain 大鼠的 Cmax = 2600 ng/ml 和 6500 ng/ml（1 小時(shí)觀察），t1/2 = 4.2 小時(shí) [7] .

產(chǎn)品性質(zhì)：

Cas No.：901119-35-5

別名：福他替尼; R788

化學(xué)名： [6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-3-oxopyrido[3,2-b][1,4]oxazin-4-yl]methyl dihydrogen phosphate

Canonical SMILES CC1(C(=O)N(C2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)COP(=O)(O)O)C

分子式：C23H26FN6O9P

分子量：580.46

溶解度：≥ 100.4mg/mL in DMSO

儲(chǔ)存條件：Store at -20°C

注意事項(xiàng)：

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References:

[1]. McAdoo S P, Tam F W K. Fostamatinib disodium[J]. Drugs of the Future, 2011, 36(4): 273.

[2]. Braselmann S, Taylor V, Zhao H, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation[J]. Journal of Pharmacology and Experimental Therapeutics, 2006, 319(3): 998-1008.

[3]. Kuiatse I, Thomas S K, Weber D M, et al. Inhibition of spleen tyrosine kinase with fostamatinib shows pre-clinical activity against models of Waldenstr?m macroglobulinemia[J]. Blood, 2012, 120(21): 3723.

[4]. Tian G, Fu Y, Zhang D, et al. Identification of four key prognostic genes and three potential drugs in human papillomavirus negative head and neck squamous cell carcinoma[J]. Cancer cell international, 2021, 21(1): 1-18.

[5]. Suljagic M, Longo P G, Bennardo S, et al. The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Eμ-TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling[J]. Blood, The Journal of the American Society of Hematology, 2010, 116(23): 4894-4905.

[6]. Young R M, Hardy I R, Clarke R L, et al. Mouse models of non-Hodgkin lymphoma reveal Syk as an important therapeutic target[J]. Blood, The Journal of the American Society of Hematology, 2009, 113(11): 2508-2516.

[7]. Pine P R, Chang B, Schoettler N, et al. Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor[J]. Clinical immunology, 2007, 124(3): 244-257.