生物活性
OSI-420 is an active metabolite of erlotinib which is an orally active EGFR tyrosin kinase inhibitor with IC50 of 2 and 20 nM for the inhibition of human EGFR and EGFR autophosphorylation in tumor cells. Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m2. OSI-420 exposure (AUC) in plasma was 30% (range 12–59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUCCSF:AUCplasma) of erlotinib and OSI-420 was <5% relative to total plasma concentration, but CSF drug exposure was ~30% of plasma free drug exposure, which was calculated from published plasma protein binding values. The intravenous administration of erlotinib was well tolerated.
化学数据
| 分子量 | 415.87 |
| 分子式 | C21H21N3O4.HCl |
| CAS号 | 183320-51-6 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO 80 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 | A549, H322, H3255, H358 H661, H1650, H1975, H1299, H596 cells |
| 方法 | Exponentially growing cells are seeded in 96-well plastic plates and exposed to serial dilutions of erlotinib, pemetrexed, or the combination at a constant concentration ratio of 4:1 in triplicates for 72 h. Using cell count and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to assay cell viability . Expressing growth inhibition as the percentage of surviving cells in drug-treated versus PBS-treated control cells (which is considered as 100% viability). The IC50 value is the concentration resulting in 50% cell growth inhibition by a 72-h exposure to drug(s) compared with untreated control cells and is calculated by the CalcuSyn software |
| 浓度 | 30 nM-20 μM |
| 处理时间 | 72 hour |
| 动物实验 |
|---|
| 动物模型 | Male 5-week-old BALB-nu/nu mice with HPAC |
| 配制 | 6% Captisol |
| 剂量 | 50 mg/kg |
| 给药处理 | Oral administration |
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 | 2.4046 mL | 12.023 mL | 24.046 mL |
| 5 mM | 0.4809 mL | 2.4046 mL | 4.8092 mL |
| 10 mM | 0.2405 mL | 1.2023 mL | 2.4046 mL |
