生物活性
CP-91149 is a human liver glycogen phosphorylase α (HLGPα) inhibitor with an IC50 of 0.13 μM in the presence of 7.5 mM glucose. CP-91149 suppressed glucagon-triggered glycogenolysis in isolated rat hepatocytes and in primary human hepatocytes. In vivo, oral injection of CP-91149 to diabetic ob/ob mice at 25–50 mg/kg led in rapid (3 h) glucose lowering by 100–120 mg/dl without producing hypoglycemia. In addition, upon treatment with CP-91149, A549 non-small cell lung carcinoma (NSCLC) cells accumulated glycogen with associated growth retardation. Treated normal skin fibroblasts also accumulated glycogen with G1-cell cycle arrest that was associated with inhibition of cyclin E-CDK2 activity. Overall, cells expressing high levels of brain GP were growth prevented by CP-91149 associating with glycogen accumulation whereas cells expressing low levels of brain GP were not affected by the agent.
化学数据
| 分子量 | 399.87 |
| 分子式 | C21H22ClN3O3 |
| CAS号 | 186392-40-5 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO 70 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 | HSF55 and T98G |
| 方法 | Exposing cells to various concentrations of CP-91149 for 72hours. Determining viability with manual cell counts following staining with trypan blue exclusion assay. Fixing cells with 70% ethanol. Staining DNA with propidium iodide and the intensity of fluorescence is measured using a Becton-Dickinson flow cytometer at 488nm for excitation and at 650nm for emission. Using Modifit's Sync Wizard is analyze the cell cycle profile . |
| 浓度 | Dissolved in DMSO, final concentrations ~50 μM |
| 处理时间 | 72 hours |
| 动物实验 |
|---|
| 动物模型 | Obese, diabetic male C57BL/6J-Lep(ob/ob) mice and their lean, nondiabetic C57BL/6J-/+ littermates |
| 配制 | Formulated in vehicle consisting of either 0.25% (wt/vol) methyl cellulose in water or 0.1% Pluronic P105 Block Copolymer Surfactant in 0.1% saline |
| 剂量 | ~50 mg/kg |
| 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）
| 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 | 2.5008 mL | 12.5041 mL | 25.0081 mL |
| 5 mM | 0.5002 mL | 2.5008 mL | 5.0016 mL |
| 10 mM | 0.2501 mL | 1.2504 mL | 2.5008 mL |
