Fostamatinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Fostamatinib（R788 二钠盐）是活性代谢物 R406 的前药，R406 是 Syk 激酶的有效 ATP 竞争性抑制剂，Ki/IC50 为 30/41 nM；剂量依赖性抑制抗 IgE 介导的 CHMC 脱颗粒，EC50 为 56 nM，抑制 Syk 信号传导下游的所有磷酸化事件；特异性抑制人类肥大细胞、巨噬细胞和中性粒细胞中的 FcγR 信号传导。 R788可以抑制免疫复合物介导的局部炎症损伤；减少关节炎模型中免疫复合物介导的炎症。

Fostamatinib (R788 disodium salt) is a prodrug of the active metabolite R406, which is a potent, ATP-competitive inhibitor of Syk kinase with Ki/IC50 of 30/41 nM; dose-dependently inhibits anti-IgE-mediated CHMC degranulation with an EC50 of 56 nM, inhibits all phosphorylation events downstream of Syk signaling; specifically inhibits FcγR signaling in human mast cells, macrophages, and neutrophils. R788 can inhibit local inflammatory injury mediated by immune complexes; reduces immune complex-mediated inflammation in arthritis models. Rheumatoid Arthritis Phase 3 Clinical(In Vivo):Fostamatinib (R788) is highly bioavailable, and rapidly absorbed in Louvain rats. R406 following a single oral dose of R788 10 mg/kg or 20 mg/kg: AUC0-16 hrs= 10618 ng*h/mL and 30650 ng*h/mL respectively; Cmax=2600 ng/mL and 6500 ng/mL respectively (observed at 1 hour); t1/2=4.2 hours. The prodrug was not detected in plasma suggesting R788 is completely converted to R406.

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R788 disodium salt | R935788

Angiogenesis

Syk

Syk

Inflammation/Immunology

Rheumatoid Arthritis

1025687-58-4

624.4232

C23H24FN6Na2O9P

>98% (HPLC)

10 mM in DMSO

[Na+].[Na+].COC1=CC(NC2=NC=C(F)C(NC3=NC4=C(OC(C)(C)C(=O)N4COP([O-])([O-])=O)C=C3)=N2)=CC(OC)=C1OC

2H-Pyrido[3,2-b]-1,4-oxazin-3(4H)-one, 6-[[5-fluoro-2-[(3,4,5-trimethoxyphenyl)amino]-4-pyrimidinyl]amino]-2,2-dimethyl-4-[(phosphonooxy)methyl]-, sodium salt (1:2)

(-20℃)

With Ice Pack

≥ 2 years