规格 | 价格 | 库存 | 数量 |
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10 mM * 1 mL in DMSO |
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5mg |
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10mg |
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100mg |
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250mg |
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500mg |
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1g |
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2g |
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5g |
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Other Sizes |
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靶点 |
PARP-2 ( IC50 = 1 nM ); PARP-1 ( IC50 = 5 nM ); tankyrase-1 ( IC50 = 1.5 μM ); Autophagy; Mitophagy
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体外研究 (In Vitro) |
体外活性:奥拉帕尼可对抗 BRCA1 或 BRCA2 突变。奥拉帕尼对坦科聚合酶 1 不敏感 (IC50 >1 μM)。浓度为 30-100 nM 的奥拉帕尼可以消除 SW620 细胞中的 PARP-1 活性。与 BRCA1 和 BRCA2 丰富的细胞系(Hs578T、MDA-MB-231 和 T47D)相比,奥拉帕尼对 BRCA1 缺陷细胞系(MDA-MB-463 和 HCC1937)高度敏感。由于PARP抑制作用抑制了碱基切除修复,奥拉帕尼对KB2P细胞高度敏感,这可能导致DNA复制过程中单链断裂转化为双链断裂,从而激活BRCA2依赖性重组途径。激酶测定:向第 1 至第 10 列中添加 1 μL 奥拉帕尼(在 DMSO 中),并且仅将 1 μL DMSO 添加至阳性 (POS) 和阴性 (NEG) 对照孔(分别为第 11 列和第 12 列)预处理的 FlashPlate。 PARP-1 在缓冲液中按 1:40 稀释(缓冲液 B:10% 甘油 (v/v)、25 mM HEPES、12.5 mM MgCl2、50 mM KCl、1 mM DTT、0.01% NP-40 (v/v)、 pH 7.6)和 40 μL 添加到所有 96 个孔中(测定中的最终 PARP-1 浓度约为 1 ng/μL)。将板密封并在室温下摇动 15 分钟。随后,将 10 μL 阳性反应混合物(每孔 0.2 ng/μL 双链寡核苷酸 [M3/M4] DNA、5 μM NAD+ 最终测定浓度和每孔 0.075 μCi 3H-NAD+)添加到适当的反应孔中。孔(第 1-11 列)。将不含 DNA 寡核苷酸的阴性反应混合物添加到第 12 列(使用平均阴性对照值作为背景)。将板重新密封并在室温下再摇动 60 分钟以使反应继续进行。然后,向每孔中加入 50 μL 冰冷的乙酸 (30%) 以终止反应,并将板密封并在室温下再摇动 60 分钟。然后使用 TopCount 读板器以每分钟计数 (CPM) 确定与 FlashPlate 结合的氚化信号。细胞测定:奥拉帕尼的细胞毒性通过克隆形成测定来测量。使用前将奥拉帕尼溶解在 DMSO 中并用培养基稀释。将细胞(乳腺癌细胞系,包括 SW620 结肠细胞、A2780 卵巢细胞、HCC1937、Hs578T、MDA-MB-231、MDA-MB-436 和 T47D)接种在六孔板中并贴壁过夜。然后添加不同浓度的奥拉帕尼并将细胞孵育7-14天。之后对存活的菌落进行计数以计算IC50。
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体内研究 (In Vivo) |
奥拉帕尼(10 mg/kg,口服)与替莫唑胺联合使用可显着抑制 SW620 异种移植物中的肿瘤生长。奥拉帕尼对 Brca1-/-;p53-/- 乳腺肿瘤显示出良好的反应(每天 50 mg/kg ip),而对 HR 缺陷的 Ecad-/-;p53-/- 乳腺肿瘤没有反应。奥拉帕尼甚至在荷瘤小鼠中没有表现出剂量限制性毒性。奥拉帕尼已用于治疗 BRCA 突变肿瘤,例如卵巢癌、乳腺癌和前列腺癌。此外,Olaparib 对 ATM(共济失调毛细血管扩张突变)缺陷型肿瘤细胞表现出选择性抑制作用,这表明它是治疗 ATM 突变淋巴肿瘤的潜在药物。
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酶活实验 |
该测定评估了奥拉帕尼抑制 PARP-1 酶活性的能力。测量 PARP-2 活性抑制的另一种方法涉及使用 PARP-2 特异性抗体在白壁 96 孔板中结合重组 PARP-2 蛋白。添加 3H-NAD+ DNA 后测量 PARP-2 活性。洗涤后添加闪烁剂以量化 3H 掺入的核糖基化。创建了针对 tankyrase-1 的 AlphaScreen 测定,包括在 384 孔 ProxiPlate 测定中与生物素化 NAD+ 一起孵育 HIS 标记的重组 TANK-1 蛋白。通过添加 α 珠子结合 HIS 和生物素标签来产生邻近信号;该信号的丢失与 TANK-1 活性抑制直接相关。每个实验至少进行三次重复。
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细胞实验 |
增强因子或 PF50 值是通过将对照生长中使用的烷化剂甲磺酸甲酯 (MMS) 的 IC50 除以 MMS 加 PARP 抑制剂的 IC50 来确定的。使用 HeLa B 细胞以固定 200 nM 浓度对 Olaparib 进行 MMS 筛选测试。在结直肠细胞系 SW620 上测试的奥拉帕尼浓度为 1、3、10、100 和 300 nM。磺胺罗丹明 B (SRB) 测定用于测量细胞生长。
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动物实验 |
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参考文献 |
分子式 |
C24H23FN4O3
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分子量 |
434.46
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精确质量 |
434.18
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元素分析 |
C, 66.35; H, 5.34; F, 4.37; N, 12.90; O, 11.05
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CAS号 |
763113-22-0
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相关CAS号 |
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外观&性状 |
White solid powder
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SMILES |
C1CC1C(=O)N2CCN(CC2)C(=O)C3=C(C=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54)F
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InChi Key |
FDLYAMZZIXQODN-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C24H23FN4O3/c25-20-8-5-15(14-21-17-3-1-2-4-18(17)22(30)27-26-21)13-19(20)24(32)29-11-9-28(10-12-29)23(31)16-6-7-16/h1-5,8,13,16H,6-7,9-12,14H2,(H,27,30)
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化学名 |
4-[[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one
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别名 |
AZD2281; Ku-0059436; AZD2281; AZD-2281; AZD 2281; KU59436; KU-59436; KU 59436; KU0059436; KU-0059436; KU 0059436; Olaparib; trade name Lynparza
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体外) |
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溶解度 (体内) |
Solubility in Formulation 1: 10 mg/mL (23.02 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 100.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (11.51 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (11.51 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (5.75 mM) (saturation unknown) in 10% DMF 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 6: ≥ 2.5 mg/mL (5.75 mM) (saturation unknown) in 10% DMF 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 7: ≥ 2.5 mg/mL (5.75 mM) (saturation unknown) in 10% DMF 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 8: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 9: ≥ 0.5 mg/mL (1.15 mM) (saturation unknown) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 10: 20 mg/mL (46.03 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 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 |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
计算结果:
工作液浓度: mg/mL;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT02446704 | Active Recruiting |
Drug: Olaparib Drug: Temozolomide |
Small Cell Lung Cancer | Zofia Piotrowska | October 13, 2015 | Phase 1 Phase 2 |
NCT03641755 | Active Recruiting |
Drug: Olaparib Drug: Sapacitabine |
Breast Cancer | Dana-Farber Cancer Institute | October 1, 2018 | Phase 1 |
NCT03047135 | Active Recruiting |
Drug: Olaparib | Prostate | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
March 1, 2017 | Phase 2 |
NCT04123366 | Active Recruiting |
Biological: Pembrolizumab Drug: Olaparib |
Solid Tumors | Merck Sharp & Dohme LLC | November 18, 2019 | Phase 2 |
NCT04076579 | Active Recruiting |
Drug: Olaparib Drug: Trabectedin |
Sarcoma Sarcoma Metastatic |
University of Michigan Rogel Cancer Center |
March 17, 2020 | Phase 2 |