生物活性
Olaparib (AZD2281, Ku-0059436)是一种选择性的PARP1/2抑制剂,IC50为5 nM/1 nM,比对Tankyrase-1的作用强300倍。Olaparib是PARP抑制剂,也作用于BRCA1或BRCA2突变。Olaparib对端锚(聚合)酶-1作用效果不大,IC50值大于。Olaparib浓度为30-100 nM作用于SW620细胞,使PARP-1失活。
化学数据
分子量 | 434.46 |
分子式 | C24H23FN4O3 |
CAS号 | 763113-22-0 |
纯度 | 99.86% |
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 |
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细胞系 | SW620 colorectal cell line |
方法 | Potentiation of MMS Cytotoxicity by 47 Determined by the Use of Sulforhodamine B Cell Growth Assays. SW620 cells were seeded in 96-well plates and were left to attach overnight. Cells were preincubated with vehicle control (DMSO) or with a single concentration of KU-0059436 (1, 3, 10, 30, 100 or 300 nM) for 1 h before the addition of increasing concentrations of MMS. Cells were incubated in the presence of each drug combination for 4 days before cell growth was quantified by the use of an SRB assay.44 Data were calculated from triplicate wells as the mean percentage of cell growth relative to KU-0059436-only wells, and (SE and IC50 were calculated by the use of XL-FIT 4 software. SW620 cells showed<24% growth inhibition (>76% cell growth)
when only KU-0059436 was used at concentrations below 300 nM (data not shown). |
浓度 | 1, 3, 10, 100 and 300 nM |
处理时间 | 4 days |
动物实验 |
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动物模型 | mouse bearing SW620 xenografted tumors |
配制 | methylcellulose/PBS |
剂量 | 10 mg/kg once daily for 5 consecutive days |
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 | 2.3017 mL | 11.5085 mL | 23.0171 mL |
5 mM | 0.4603 mL | 2.3017 mL | 4.6034 mL |
10 mM | 0.2302 mL | 1.1509 mL | 2.3017 mL |