Fostamatinib (R788)
(Synonyms: 福他替尼; R788) 目录号 : GC11044
Fostamatinib (R788) 是活性化合物 R406 的口服前药，R406 是一种相对选择性的 Syk 小分子抑制剂。
Cas No.:901119-35-5
Sample solution is provided at 25 µL, 10mM.
Fostamatinib (R788) is the oral prodrug of the active compound R406, a relatively selective small molecule inhibitor of Syk [1]. R406 is a competitive inhibitor for ATP binding to the Syk catalytic domain (Ki = 30 nM), and inhibits Syk kinase activity in vitro with an IC50 of 41 nM [2].
Fostamatinib (R788) induced a time- and dose-dependent reduction in viability of Waldenstr?m macroglobulinemia (WM) MWCL-1 and BWCM.1 cells, with IC50 that were in the physiologically relevant range of approximately 0.25 and 1 μM, respectively, at 3 days [3]. Fostamatinib (R788) greatly inhibited the proliferation of six HPV-negative HNSCC cell lines in vitro [4].
Fostamatinib (R788) (80 mg/kg/d, 21d) significantly prolonged the survival of mice challenged with the leukemia lines TCL1-551 and TCL1-870 [5]. Fostamatinib (R788)(80 mg/kg/d, 7d) has shown efficacy in murine models of non-Hodgkin`s lymphoma (NHL), reducing tumour burden and prolonging survival in treated mice [6]. A single oral dose of R788 10 mg/kg or 20 mg/kg: Cmax = 2600 ng/ml and 6500 ng/ml respectively (observed at 1 hour), t1/2 = 4.2 hours in Louvain rats [7].
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.
Fostamatinib (R788) 是活性化合物 R406 的口服前药，R406 是一种相对选择性的 Syk 小分子抑制剂[1]。 R406 是 ATP 结合 Syk 催化结构域 (Ki = 30 nM) 的竞争性抑制剂，在体外抑制 Syk 激酶活性，IC50 为 41 nM [2]。
Fostamatinib (R788) 诱导 WaldenstrÖm 巨球蛋白血症 (WM) MWCL-1 和 BWCM.1 细胞的存活时间和剂量依赖性降低，IC50 分别在大约 0.25 和 1 μM 的生理相关范围内，第 3 天 [3]。 Fostamatinib (R788) 在体外显着抑制了 6 种 HPV 阴性 HNSCC 细胞系的增殖[4]。
Fostamatinib (R788)（80 mg/kg/d，21 天）显着延长了受到白血病细胞系 TCL1-551 和 TCL1-870 攻击的小鼠的存活时间 [5]。 Fostamatinib (R788)（80 mg/kg/d，7 天）在非霍奇金淋巴瘤 (NHL) 小鼠模型中显示出疗效，可减轻治疗小鼠的肿瘤负荷并延长生存期[6] .单次口服 R788 10 mg/kg 或 20 mg/kg:Louvain 大鼠的 Cmax = 2600 ng/ml 和 6500 ng/ml（1 小时观察），t1/2 = 4.2 小时 [7] .
| Cell experiment [1]: | |
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Cell lines |
Head and neck squamous cell carcinoma (HNSCC) HN4, HN6, HN30, SCC9, SCC25 and CAL27 cell lines |
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Preparation Method |
Approximately 3 × 103 cells per well were seeded in 96-well culture plates. After culture for 24 h, the medium was removed. Fostamatinib (R788) at different concentrations were added with the volume of 100 µl. For the negative control wells, drug-free medium was added and cultured for 72 h. |
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Reaction Conditions |
0-106 nM for 72 hours |
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Applications |
The proliferation of all cell lines was inhibited by Fostamatinib, The IC50 values of fostamatinib was range from 0.811 to 3.470 µM. |
| Animal experiment [2]: | |
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Animal models |
Female NZB/NZW mice |
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Preparation Method |
Prediseased NZB/NZW mice (urinary protein level |
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Dosage form |
0, 10, 20, 30, 40 mg/kg twice daily for 240 days. |
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Applications |
2 of 29 mice treated with the 40-mg/kg dose of fostamatinib demonstrated elevated proteinuria (urinary protein level >300 mg/dl), compared with 21 of 30 mice in the vehicle-treated group. All 29 mice treated with 40 mg/kg of R788 survived until study termination . |
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References: [1]: 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. |
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| Cas No. | 901119-35-5 | SDF | |
| 别名 | 福他替尼; R788 | ||
| 化学名 | [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 | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7228 mL | 8.6139 mL | 17.2277 mL |
| 5 mM | 0.3446 mL | 1.7228 mL | 3.4455 mL |
| 10 mM | 0.1723 mL | 0.8614 mL | 1.7228 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet