CAS:763113-22-0
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to yellow Solid
是一种有效的 PARP 抑制剂。
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OlaparibCAS:763113-22-0
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to yellow Solid
CAS | 763113-22-0 |
Chinese Name | 奥拉帕尼 |
English Name | Olaparib |
Synonyms | KU0059436;AZD2281 |
Molecular Formula | C24H23FN4O3 |
Molecular Weight | 434.46 |
Solubility | Soluble in DMSO |
Purity | ≥98% |
Appearance | White to yellow Solid |
Storage | Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
EC | EINECS 642-941-5 |
MDL | MFCD13185161 |
SMILES | O=C(C1=CC(CC(C2=C3C=CC=C2)=NNC3=O)=CC=C1F)N4CCN(C(C5CC5)=O)CC4 |
Target Point | PARP |
Passage | Cell Cycle;DNA Damage/DNA Repair; Epigenetics |
Background | Olaparib is a potent PARP inhibitor. |
Biological Activity | Olaparib 是一种有效的 PARP 抑制剂,抑制 PARP-1 和 PARP-2 的 IC50 分别为 5 和 1 nM[1-4]。 |
IC50 | PARP-2:1nM;PARP-1:5nM;tankyrase-1:1.5μM [1-4] |
In Vitro | Olaparib是PARP-1和PARP-2的单位数纳摩尔抑制剂,显示出对抗BRCA1缺陷的乳腺癌细胞系的独立活性。 Olaparib应用于SW620细胞裂解液,并确定PARP-1抑制的IC50约为6 nM,PARP-1活性的总消融浓度为30-100 nM [1]。 |
In Vivo | 携带SW620异种移植肿瘤的动物用奥拉帕尼(10mg/kg,口服)与替莫唑胺(TMZ)(50mg/kg,口服)联合治疗,每天一次,连续5天,之后使肿瘤生长[1] ]。 Olaparib增加了在DWC模型中建立的Calu-6肿瘤中的血管灌注。给予奥拉帕尼(50mg/kg,口服)作为单一药剂(上图)或与辐射组合(下图)导致Calu-6肿瘤中荧光强度的增加[2]。 |
Cell Experiment | PF50值是增强因子,其计算为对照生长与烷基化剂甲基甲磺酸盐(MMS)的IC50除以MMS与PARP抑制剂组合的IC50的比率。使用HeLa B细胞,并以固定的200nM浓度测试Olaparib用于MMS筛选。对于在SW620结肠直肠细胞系上测试Olaparib,使用的浓度为1,3,10,100和300nM。通过使用磺酰罗丹明B(SRB)测定评估细胞生长[1]。 |
Animal Experiment | 小鼠[2]将携带220-250mm 3肿瘤的小鼠随机分成4个治疗组(n = 5):A;载体对照(PBS中10%DMSO/10%2-羟基 - 丙基-β-环糊精,每天口服强饲5天),B;奥拉帕尼(通过口服强饲法每天50mg/kg,持续5天),C; 10 Gy分次放疗(每日2 Gy,连续5天),D; Olaparib和10 Gy(5×2 Gy)分次放疗(每天2 Gy剂量放射前30分钟给予olaparib)。每天测定肿瘤体积测量值,直至达到1000mm 3。对于每组中的个体肿瘤,计算每个肿瘤从治疗开始时的四倍大小的天数(相对肿瘤体积×4; RTV4)。 |
Kinase Experiment | 该测定确定了奥拉帕尼抑制PARP-1酶活性的能力。通过使用PARP-1测定的变体测量PARP-2活性抑制,其中PARP-2蛋白(重组体)在96孔白壁板中被PARP-2特异性抗体结合。在3H-NAD + DNA添加后测量PARP-2活性。洗涤后,加入闪烁剂以测量掺入3H的核糖基化。对于端锚聚合酶-1,开发了AlphaScreen测定法,其中在384孔ProxiPlate测定中将HIS标记的重组TANK-1蛋白与生物素化的NAD +一起温育。添加α珠以结合HIS和生物素标签以产生接近信号,而TANK-1活性的抑制与该信号的损失成正比。所有实验至少重复三次[1]。 |
Data Literature Source | [1]. Menear KA,et al. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem. 2008 Oct 23;51(20):6581-91 [2]. Senra JM,et al. Inhibition of PARP-1 by olaparib (AZD2281) increases the radiosensitivity of a lung tumor xenograft.Mol Cancer Ther. 2011 Oct;10(10):1949-58. [3]. Yasukawa M,et al. Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo. Int J Mol Sci. 2016 Feb 24;17(3):272. [4]. Bian X,et al. PTEN deficiency sensitizes endometrioid endometrial cancer to compound PARP-PI3K inhibition but not PARP inhibition as monotherapy. Oncogene. 2018 Jan 18;37(3):341-351 |
Unit | Piece |
Specification | 5mg 10mg 50mg |
是一种有效的 PARP 抑制剂。