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。此外，Olaparib 也是PARP-1依赖性细胞死亡（parthanatos）抑制剂，以及自噬 (autophagy) 和线粒体自噬 (mitophagy) 激活剂。具有广谱的抗癌活性，可用于卵巢癌的相关研究。
别名：Olaparib; KU-0059436
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。Olaparib 也是PARP-1依赖性细胞死亡（parthanatos）抑制剂，以及自噬 (autophagy) 和线粒体自噬 (mitophagy) 激活剂。
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数据来源 | Int J Biol Sci (2018 Oct). Figure 5. Olaparib (Abmole Bioscience, Houston, USA) |
| 方法 | IP | |
| 细胞系/动物模型 | mice | |
| 浓度 | 100 mg/kg | |
| 处理时间 | - | |
| 实验结果 | The overall RTVs (treated vs. non-treated tumors) for mice bearing Brca1-mutant tumor allografts were 60.8% and 62.6% for mice treated with MK-2206 and olaparib, respectively. |
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数据来源 | Int J Biol Sci (2018 Oct). Figure 4. Olaparib (Abmole Bioscience, Houston, USA) |
| 方法 | IP | |
| 细胞系/动物模型 | mice | |
| 浓度 | 100 mg/kg | |
| 处理时间 | - | |
| 实验结果 | In mice co-treated with olaparib and MK-2206, tumor volume was only increased ~1.8-fold at this same time, indicating that these agents exerted a additive effect on tumor growth. |
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数据来源 | Int J Oncol (2015). Figure 4. AZD2281 |
| 方法 | apoptosis assay | |
| 细胞系/动物模型 | HCC‑1428 cells | |
| 浓度 | 2 μM | |
| 处理时间 | 4 day | |
| 实验结果 | Inhibition of autophagy by knocking down ATG5 also partially inhibited AZD2281-induced apoptosis, suggesting that autophagy contributes to AZD2281-induced cell death in BRCA mutated breast cancer cells. |
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数据来源 | Int J Oncol (2015). Figure 1. AZD2281 |
| 方法 | Transmission electron microscopy | |
| 细胞系/动物模型 | BRCA1 or BRCA2 mutant breast cancer cell lines | |
| 浓度 | 2 μM | |
| 处理时间 | 4 day | |
| 实验结果 | The growth inhibition effect of AZD2281 was significantly higher in the BRCA wild-type cell lines with BRCA1 allelic loss than in the BRCA wild-type cell line without BRCA1 allelic loss. |
| 体外实验* | |
|---|---|
| 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 |
*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
| 体内实验* | |
|---|---|
| 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 |
*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
| 分子量 | 434.46 |
| 分子式 | C24H23FN4O3 |
| CAS号 | 763113-22-0 |
| 溶解性（25°C） | DMSO 90 mg/mL DMF 45 mg/mL |
| 储存条件 |
粉末型式 -20°C 3年；4°C 2年 溶于溶剂 -80°C 6个月；-20°C 1个月 |
| 运输方式 | 冰袋运输，根据产品的不同，可能会有相应调整。 |
*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 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 |
| 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。
[5] Marchetti et al. Expert Opin Investig Drugs. Olaparib , PARP1 inhibitor in ovarian cancer.
| 其他相关的PARP产品 |
|---|
| DSB-1522
DSB-1522是一种PARP1抑制剂，可用于肿瘤的相关研究。 |
| DM-5167
DM-5167是一种PARP1抑制剂，可用于三阴性乳腺癌的相关研究。 |
| NMS-03305293
NMS-03305293是一种PARP抑制剂，对PARP1亚型有高选择性，DNA捕获效应较低，可特异性杀伤BRCA突变的肿瘤细胞。此外，NMS-03305293还可穿透血脑屏障，可用于中枢神经肿瘤和脑转移肿瘤的相关研究。 |
| SNV1521
SNV1521是一种潜在同类最佳的（best-in-class），高选择性和中枢神经系统渗透性PARP1抑制剂。 |
| Basroparib
Basroparib是一种具有口服活性的端锚聚合酶（TNKS）选择性抑制剂，同时也是核糖聚合酶 (PARP) 抑制剂，具有抗肿瘤活性。 |
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