| 名称 | Niraparib |
| 描述 | Niraparib (MK-4827) is a PARP inhibitor that selectively inhibits PARP1 and PARP2 (IC50=3.8/2.1 nM). Niraparib has antitumor activity, inhibits DNA damage repair, and induces apoptosis. |
| 细胞实验 | Proliferation assays were conducted in 96-well black viewplates, and 300 cells/well (250 cell/well for BRCA-1 wt) in culture medium, 190 μL/well (DMEM containing 10% FCS, 0.1 mg/mL penicillin-streptomycin, and 2 mM L-glutamine), were plated and incubated for 4 h at 37℃ under 5% CO2 atmosphere. Inhibitors were then added with serial dilutions, 10 μL/well to obtain the desired final compound concentration in 0.5% DMSO. The cells were then incubated for 7 days at 37℃ in 5% CO2 after which time viability was assessed. Briefly, with CellTiter-Blue solution prediluted 1:10 in medium, 100 μL/well was added and the cells left for 45 min at 37℃ under 5% CO2 and then a further 15 min at room temperature in the dark. The number of living cells was determined by reading the plate at fluorimeter, excitation at 550 nm and emission at 590 nm. Cell growth was expressed as the percentage growth with respect to vehicle treated cells. The concentration required to inhibit cell growth by 50% (CC50) was determined.(Only for Reference) |
| 激酶实验 | Enzyme assay is conducted in buffer containing 25 mM Tris, pH 8.0, 1 mM DTT, 1 mM spermine, 50 mM KCl, 0.01% Nonidet P-40, and 1 mM MgCl2. PARP reaction contains 0.1 μCi [3H]NAD+ (200?000 DPM), 1.5 μM NAD+, 150 nM biotinylated NAD+, 1 μg/mL activated calf thymus, and 1?5 nM PARP-1. Autoreactions utilizing SPA bead-based detection are carried out in 50 μL volumes in white 96-well plates. Compounds (e.g., MK-4827) are prepared in 11-point serial dilution in 96-well plate, 5 μL/well in 5% DMSO/Water (10× concentrated). Reactions are initiated by adding first 35 μL of PARP-1 enzyme in buffer and incubating for 5 min at room temperature and then 10 μL of NAD+ and DNA substrate mixture. After 3 h at room temperature, these reactions are terminated by the addition of 50 μL of streptavidin-SPA beads (2.5 mg/mL in 200 mM EDTA, pH 8). After 5 min, they are counted using a TopCount microplate scintillation counter. IC50 data is determined from inhibition curves at various substrate concentrations[1]. |
| 体外活性 | 方法：PDAC 细胞系 MIA-PaCa-2、PANC-1、Capan-1 和 OvCa 细胞系 OVCAR8、PEO1 用 Niraparib (0.1-200 µM) 处理 48 h，使用 CellTiter-Glo Luminescent Cell Viability Assay 检测细胞活力。
结果：Niraparib 对 MIA-PaCa-2、PANC-1、Capan-1、OVCAR8、PEO1 细胞的 IC50 分别为 26 µm、50 µm、15 µM、20 µM 和 28 µM。[1]
方法：卵巢癌细胞 SKOV3 和 UWB1.289 用 Niraparib (0.5-15 µM) 处理 48 h，使用 Western Blot 方法检测靶点蛋白表达水平。
结果：Niraparib 上调了 SKOV3 和 UWB1.289 细胞中 PD-L1 的表达。[2] |
| 体内活性 | 方法：为检测体内抗肿瘤活性，将 Niraparib (25 mg/kg，口服给药，每周四次) 和 PD-L1 (10mg/kg，腹腔注射，每周两次) 给药给携带卵巢癌肿瘤 ID8 的 C57BL/6 小鼠，持续八周。
结果：Niraparib 在体内上调卵巢肿瘤的 PD-L1 表达，并与 PD-L1 阻断具有协同作用。[2]
方法：为检测体内抗肿瘤活性，将 Niraparib (50 mg/kg，0.5% methylcellulose) 灌胃给药给携带颅内人源性 TNBC 细胞系 SUM149、MDA-MB-231Br 或 MDA-MB-436 的 C57BL/6 小鼠，每天一次，持续两周。
结果：在 BRCA 突变型 MDA-MB-436 模型中，Niraparib 增加中位生存期和减少肿瘤负荷。但在 BRCA 突变型 SUM149 或 BRCA 野生型 MDA-MB-231Br 模型中不增加，尽管颅内肿瘤中存在高浓度。[3] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | Ethanol : 60 mg/mL (187.27 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 6 mg/mL (18.73 mM), Solution.
DMSO : 65.63 mg/mL (204.84 mM), Sonication is recommended.
|
| 关键字 | V-PARP | TANK-1 | poly ADP ribose polymerase | PARP3 | PARP2 | PARP1 | PARP | ovarian | orally | Niraparib | MK4827 | MK 4827 | lung | Inhibitor | inhibit | DNA | damage | cancer | breast | bioavailable | Apoptosis | anti-tumor |
| 相关产品 | Urea | Dimethyl phthalate | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Metronidazole | Dextran sulfate sodium salt (MW 5000) | Citric Acid Triammonium | Gum arabic | Stavudine | Tamoxifen | Sodium 4-phenylbutyrate |
| 相关库 | 抑制剂库 | 抗癌活性化合物库 | 经典已知活性库 | 抗癌上市药物库 | 已知活性化合物库 | 临床失败化合物库 | 高选择性抑制剂库 | 抗衰老化合物库 | FDA 上市药物库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |