生物活?/h4>
Fostamatinib (R788)是活性代谢产物R406的前体药物，是一种Syk抑制剂，IC50?1 nM，强效抑制Syk但不抑制Lyn，对Flt3作用效果?倍。R935788是R406亚甲基磷酸言药物前体,可在体内快速转化为R406。R406(R935788的活性形?选择性抑制Syk依赖性信号，EC50?3 nM ?71 nM,比作用于Syk非依赖性通路更有效。R406抑制多种弥散性大B细胞淋巴?DLBCL)细胞系增殖，EC50 0.8 μM?.1 μM。R406 处理，降低BLNK, Akt, GSK-3, FOXO和ERK 磷酸化。此? R406作用于TCL1白血病，完全抑制?IgM抗体诱导的BCR信号。尽管TCL1白血病中存在高水平的组成型激活的Syk，但是R406对白血病细胞没有选择毒性、/p>
化学数据
| 分子野/td> |
580.46 |
| 分子弎/td> |
C23H26FN6O9P |
| CAS叶/td> |
901119-35-5 |
| 纯度 |
99.55% |
| 溶解性（25C（/td> |
DMSO 96 mg/mL |
| 储存和运输条仵/td> |
固体粉末 -20C 冷藏长期储存
常温运输及临时存攽/td> |
实验操作来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
| 细胞糺/td> |
Cultured human mast cells (CHMC) |
| 方法 |
Human Mast Cell Culture and Stimulation.
Cultured human mast cells (CHMC) were derived from cord blood CD34+ progenitor cells and grown, primed, and stimulated as described previously (Rossi et al., 2006) and shown in supplemental data. Before stimulation, cells were incubated with R406 or DMSO for 30 min. Cells were 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 were stimulated for 30 min in modified Tyrode's buffer. For LTC4 and cytokine production, 100,000 cells per well were stimulated for 1 or 7 h, respectively. Tryptase activity was measured by luminescence readout of a peptide substrate, and LTC4 and cytokines were measured using Luminex multiplex technology. |
| 浓度 |
0~20 μM |
| 处理时间 |
30 min |
| 动物实验 |
| 动物模型 |
K/BxN Model Arthritis induced in C57BL/6 mice |
| 配制 |
35% TPGS, 60% PEG 400, and 5% propylene glycol |
| 剂量 |
5 and 10mg/kg b.i.d for 13 days |
| 给药处理 |
orally |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南（/h4>
|
小鼠 |
大鼠 |
兓/td> |
豚鼠 |
仓鼠 |
狖/td> |
| 重量 (kg) |
0.02 |
0.15 |
1.8 |
0.4 |
0.08 |
10 |
| 体表面积 (m2) |
0.007 |
0.025 |
0.15 |
0.05 |
0.02 |
0.5 |
| Km系数 |
3 |
6 |
12 |
8 |
5 |
20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × |
动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数?），再除以大鼠的Km系数?），得到化合物用于大鼠的等效剂量?0 mg/kg、/p>
储备液配刵/h4>
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作、/p>
| Concentration / Solvent Volume / Mass |
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 |
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