Fostamatinib disodium hexahydrate (福他替尼二钠盐六水合物,R788 disodium hexahydrate)
国际站:Fostamatinib disodium hexahydrate
CAS:914295-16-2
纯度:99.73%
分子量:732.51
Formula:C23H36FN6Na2O15P
运输条件:Room temperature in continental US; may vary elsewhere.
储存方式:
4°C, sealed storage, away from moisture
*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
产品活性:Fostamatinib (R788) disodium hexahydrate 是 R406 的口服前体。R406 是一种有效的,具有口服活性的,ATP 竞争性的 Syk/FLT3 抑制剂,Ki 为 30 nM,IC50 为 41 nM。R406 还抑制 Lyn (IC50=63 nM) 和 Lck (IC50=37 nM).
生物活性:福司他替尼(R788)六水二钠是活性化合物R406的口服前驱剂[1]。R406是一种口服有效的竞争性Syk/FLT3抑制剂,Ki为30 nM, IC50为41 nM[2]。R406也抑制Lyn (IC50=63 nM)和Lck (IC50=37 nM)[3]。
体内:Fostamatinib (R788)生物利用度高,在鲁汶大鼠体内吸收迅速。R406单次口服R788 10mg /kg或20mg /kg后:AUC0-16小时分别= 10618 ng*h/mL和30650 ng*h/mL;Cmax分别=2600 ng/mL和6500 ng/mL(1小时观察);t1/2 = 4.2小时。血浆中未检测到前药,提示R788完全转化为R406[1]。
参考文献:
[1]. Stephen P McAdoo, et al. Fostamatinib Disodium. Drugs Future. 2011;36(4):273.
[2]. Sylvia Braselmann, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008.
[3]. Hoon-Suk Cha , et al. A novel spleen tyrosine kinase inhibitor blocks c-Jun N-terminal kinase-mediated gene expression in synoviocytes. J Pharmacol Exp Ther. 2006 May;317(2):571-8.