生物活性
AS-604850 is a selective, ATP-competitive PI3Kγ inhibitor with IC50 of 0.25, >20, >20, and 4.5 μM for the human recombinant γ, δ, β, and α isoforms, respectively. AS-604850 shows no notable activity against a wide array of protein kinases at 1 μM. AS-604850 inhibited MCP-1-mediated monocyte chemotaxis with an IC50 value of 21 μM and reduced RANTES-induced peritoneal neutrophil recruitment in a murine model of leukocyte chemotaxis with an ED50 value of 42.4 mg/kg.
化学数据
| 分子量 | 285.22 |
| 分子式 | C11H5F2NO4S |
| CAS号 | 648449-76-7 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO 47 mg/mL |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
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 |
|---|
| 细胞系 | HepG2 Ntcp and Huh7-Ntcp cells |
| 方法 | Treating hepatocyte cultures with diluent (DMSO), 25 μM TLC, 250 μM TCDC, 50 μM GCDC, or 50 ng/ml Fas for 2-4 hours HepG2-Ntcp and treating Huh7-Ntcp cells with DMSO, 20 μM TLC, 75 μM TCDC or GCDC, 200 μM etoposide or 200 ng/ml TNFa plus 28 ng/ml actinomycin D for 2-4 hours. Using fluorescent staining to determine morphologically the number of apoptotic cells expressing as % of cells . Apoptosis is confirmed in human cell lines by determination of caspase-3/-7 activity and in rat hepatocytes by detection of the 17 kDa proteolytic cleavage fragment of caspase-3 by immunoblotting; equal protein loading is monitored by immunoblotting for actin. |
| 浓度 | 2.5 μM |
| 处理时间 | 2 - 4 hours |
| 动物实验 |
|---|
| 动物模型 | RANTES (0.5 mg/kg in 200 ml saline) or thioglycollate (40 ml/kg) are intraperitoneally injected to C3H mice to induce peritonitis mouse models |
| 配制 | AS-604850 is dissolved in vehicle (0.5% carboxymethylcellulose/0.25% Tween-20) and adjusted the solution to 10 mL/kg of body weight. |
| 剂量 | 0, 1, 3, 10 or 30 mg/kg for RANTES, 10 mg/kg for thioglycollate |
| 给药处理 | Oral administration 30 or 15 minutes before injection of RANTES or thioglycollate |
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）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 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（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
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。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.5061 mL | 17.5303 mL | 35.0607 mL |
| 5 mM | 0.7012 mL | 3.5061 mL | 7.0121 mL |
| 10 mM | 0.3506 mL | 1.753 mL | 3.5061 mL |
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