生物活性
A-966492是一种新型有效的PARP1和PARP2抑制剂，Ki分别为1 nM和1.5 nM。A-966492是最有效的PARP抑制剂之一。在所有细胞实验中，A-966492有效抑制PARP-1，EC50为1nM，Ki值为1 nM，作用于PARP-2时，Ki值为1.5 nM。A-966492作用于PARP酶具有极好的药效,尤其作用于C41细胞。
化学数据
| 分子量 | 324.35 |
| 分子式 | C18H17FN4O |
| CAS号 | 934162-61-5 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO 60 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 | C41 cell |
| 方法 | Treating C41 cells with A-966492 for 30 minutes in a 96-well plate . Activating PARP by damaging DNA with 1 mM H2O2 for 10 minutes. Washing cells with ice-cold phosphate-buffered saline (PBS) once and fixing with prechilled methanol/acetone (7:3) at -20 °C for 10 minutes. When they are air-dried, rehydrating plates with PBS and blocked using 5% nonfat dry milk in PBS-Tween(0.05%) (blocking solution) for 30 minutes at room temperature. Incubating cell with anti-PAR antibody 10H (1:50) in blocking solution at room temperature for 60 minutes followed by washing with PBS-Tween20 five times, and incubation with goat antimouse fluorescein 5(6)-isothiocyanate (FITC)-coupled antibody (1:50) and 1 μg/mL 40,6-diamidino-2-phenylindole (DAPI) in blocking solution at room temperature for 60 minutes. After washing with PBS-Tween20 5 times, using an fmax Fluorescence Microplate Reader set at the excitation and emission wavelength for FITC or the excitation and emission wavelength for DAPI to perform analysis. Normalizing PARP activity (FITC signal) with cell numbers (DAPI). |
| 浓度 | ~10 nM |
| 处理时间 | 30 minutes |
| 动物实验 |
|---|
| 动物模型 | A 0.2 cc amount of a 1:10 dilution of tumor brei in 45% Matrigel and 45% Spinner MEM is injected subcutaneously into the flank of female SCID mice. |
| 配制 | |
| 剂量 | 12.5, 25, and 50 mg/kg/day, for 14 days |
| 给药处理 | Orally administrated |
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 | 3.0831 mL | 15.4154 mL | 30.8309 mL |
| 5 mM | 0.6166 mL | 3.0831 mL | 6.1662 mL |
| 10 mM | 0.3083 mL | 1.5415 mL | 3.0831 mL |
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