奥拉帕尼 T3015

Product Introduction
Bioactivity


英文名: Olaparib

描述: Olaparib (KU0059436) 是 PARP1/PARP2 的小分子抑制剂 (IC50=5/1 nM)，对 PARP tankyrase-1 的抑制活性较弱 (IC50=1.5 μM)，具有选择性和口服活性。Olaparib 具有自噬和线粒体自噬激活活性。

细胞实验: HSC-2, Ca9-22, and SAS oral carcinoma cells were seeded in 24-well plates at a density of 2 × 104 cells/well. After overnight incubation, the culture medium was replaced with fresh medium containing various concentrations of PARP inhibitor AZD228 or cisplatin. After 24 h of treatment, the number of viable cells was assessed using an MTT assay as reported previously. Briefly, one-tenth of the fluid volume of 5 mg/mL MTT in RPMI-1640 medium was added to each well, followed by incubation for 4 h at 37 °C. After incubation, the medium was carefully removed and an adequate volume of 0.1 N HCl in isopropanol was added to each well and the resultant formazan crystals was dissolved. Absorbance was determined at 570 nm by microplate reader in 96-well assay plates. All experiments were performed in triplicate [2].

激酶实验: This assay determined the ability of test compounds to inhibit PARP-1 enzyme activity. The method that was used was as reported. We measured PARP-2 activity inhibition by using a variation of the PARP-1 assay in which PARP-2 protein (recombinant) was bound down by a PARP-2 specific antibody in a 96-well white-walled plate. PARP-2 activity was measured following 3H-NAD+ DNA additions. After washing, scintillant was added to measure 3 H-incorporated ribosylations. For tankyrase-1, an AlphaScreen assay was developed in which HIS-tagged recombinant TANK-1 protein was incubated with biotinylated NAD+ in a 384-well ProxiPlate assay. Alpha beads were added to bind the HIS and biotin tags to create a proximity signal, whereas the inhibition of TANK-1 activity was directly proportional to the loss of this signal. All experiments were repeated at least three times [1].

动物实验: Once the tumor diameter had reached 7 mm, the mice were randomly assigned to the following groups: (a) control (200 μL saline); (b) cisplatin (2 mg/kg per body weight, dissolved in 200 μL sterilized water); (c) AZD2281 (25 mg/kg per body weight, dissolved in 200 μL sterilized water); or (d) combination (both cisplatin and AZD2281). The chemicals were administered intraperitoneally every three days, five times. Although AZD2281 is administered orally in the clinic, intraperitoneal injection was recommended by the manufacturer because of easier manipulation and the ethical constraints associated with oral gavage administration to mice. Tumor size and body weight were measured at the time of administration. The tumor volume was calculated using following equation. Tumor volume = verticality × width × height × 0.5236. Three days after the last administration, all surviving mice were sacrificed [2].

体外活性: 方法：人子宫颈癌细胞 SiHa 和 ME180 用 Olaparib (5-10 µM) 和 cisplatin (1-30 µM) 处理 72 h，使用 MTT 方法检测细胞生长抑制情况。结果：Olaparib 和 cisplatin 共同处理比用单一药物处理的细胞显示出显著的细胞生长抑制作用。[1]方法：人子宫内膜癌细胞 HEC-6 和 HEC-6-PTEN 用 Olaparib (10 μM) 处理 72 h，使用 Flow Cytometry 方法分析细胞周期情况。结果：Olaparib 诱导 HEC-6 和 HEC-6-PTEN 细胞显著增加了亚 G1 群体。[2]方法：鸡淋巴瘤细胞 DT40 用 Olaparib (0.01-10 μM) 处理 30 min，使用 Western Blot 方法检测靶点蛋白表达水平。结果：Olaparib 剂量依赖性抑制 PARylation 的表达水平，抑制 PARP 的活化。[3]

体内活性: 方法：为检测体内抗肿瘤活性，将 Olaparib (10 mg/kg) 和 TMZ (50 mg/kg) 口服给药给携带人结直肠癌肿瘤 SW620 的小鼠，每天一次，持续五天。结果：与单独 TMZ 组相比，TMZ 加 Olaparib 组合治疗组观察到肿瘤体积的显著抑制。[4]方法：为研究 Olaparib 对哮喘的治疗作用，将 Olaparib (1-10 mg/kg) 腹腔注射给基于 OVA 的哮喘 C57BL/6 小鼠模型，每天一次，持续三天。结果：Olaparib 能显著减少气道嗜酸性粒细胞增多、粘液产生和高反应性。Olaparib 的保护作用与抑制 Th2 细胞因子 eotaxin、IL-4、IL-5、IL-6、IL-13 和 M-CSF 以及卵清蛋白特异性 IgE 有关，同时增加 Th1 细胞因子 IFN-γ。Olaparib 有可能成为人类哮喘临床试验的候选药物。[5]

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 50 mg/mL (115.09 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
5% DMSO+95% Saline : 4 mg/mL (9.21 mM, suspension)


关键字: PARP | Mitochondrial Autophagy | inhibit | Autophagy | orally | Inhibitor | PARP1 | Mitophagy | poly ADP ribose polymerase | PARP2 | KU 0059436 | Olaparib | AZD-2281 | AZD 2281 | KU-0059436

相关产品: Vorinostat | 5-Aminolevulinic acid hydrochloride | Oxidopamine hydrobromide | Adezmapimod | Mdivi-1 | Ruxolitinib phosphate | Doxazosin mesylate | Tripterin | ABT-737 | Brefeldin A

相关库: Drug Repurposing Compound Library | Approved Drug Library | Anti-Cancer Drug Library | Inhibitor Library | Anti-Cancer Clinical Compound Library | Highly Selective Inhibitor Library | Anti-Cancer Active Compound Library | Anti-Cancer Approved Drug Library | EMA Approved Drug Library | Anti-Cardiovascular Disease Compound Library

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途