生物活性
PF-04691502是一种ATP竞争性的PI3K(α/β/δ/γ)/mTOR双重抑制剂,Ki为1.8 nM/2.1 nM/1.6 nM/1.9 nM和16 nM,对Vps34, AKT, PDK1, p70S6K, MEK, ERK, p38和JNK几乎没有作用活性。
化学数据
分子量 | 425.48 |
分子式 | C22H27N5O4 |
CAS号 | 1013101-36-4 |
纯度 | 98.68% |
溶解性(25°C) | DMSO 13 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 |
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细胞系 | BT20, U87MG, and SKOV3 cells |
方法 | Cell proliferation assays. BT20, U87MG, and SKOV3 cells were plated at 3,000 cell/well in 96-well culture plates in growth medium with 10% FBS. Cells were incubated overnight and treated with DMSO (0.1% final) or serial diluted compound for 3 days. Resazurin was added to 0.1 mg/mL. Plates were incubated at 37°C in 5% CO2 for 3 hours. Fluorescence signals were read as emission at 590 nm after excitation at 530 nm. IC50 values were calculated by plotting fluorescence intensity to drug concentration in nonlinear curves. |
浓度 | 0~1000 nM |
处理时间 | 3 days |
动物实验 |
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动物模型 | SKOV3, U87MG, or NSCLC cells tumour xenograft models in Female nu/nu mice (6–8 weeks old) |
配制 | 0.5% methylcellulose in water suspension |
剂量 | 0.5, 1, 5, and 10 mg/kg once daily |
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 |
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1 mM | 2.3503 mL | 11.7514 mL | 23.5029 mL |
5 mM | 0.4701 mL | 2.3503 mL | 4.7006 mL |
10 mM | 0.235 mL | 1.1751 mL | 2.3503 mL |