| 名称 | Niraparib tosylate |
| 描述 | Niraparib tosylate (MK-4827 (tosylate))(with IC50 of 3.8 nM/2.1 nM) is a selective PARP1/PARP2 inhibitor. |
| 细胞实验 | V-C8 (BRCA2-negative) Chinese hamster cells are treated with the PARP inhibitor MK-4827 for 24 h, washed and incubated in drug-free medium for 5-7 days until colonies formed. (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 | Micromolar concentrations of niraparib radiosensitizes tumor cell lines derived from lung, breast, and prostate cancers independently of their p53 status but not cell lines derived from normal tissues. Niraparib also sensitizes tumor cells to Water2 and converts Water2-induced single strand breaks (SSBs) into DSBs during DNA replication[5]. |
| 体内活性 | Niraparib tosylate strongly enhances the effect of radiation on a variety of human tumor xenografts, both p53 wild type and p53 mutant. Niraparib tosylate reduces PAR levels in tumors by 1 h after administration which persisted for up to 24 h[1]. In vivo treatment with Niraparib tosylate and radiation prolonged survival (p<0.01) compared to single modalities. In vivo superiority of Niraparib tosylate plus radiation is further documented by significant elevations of cleaved caspase-3 and γ-H2AX in tumors from the combination group compared to single modality cohorts[4]. |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 91 mg/mL (184.7 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 关键字 | PARP | Niraparib tosylate | Apoptosis | inhibit | MK-4827 Tosylate | MK4827 | Niraparib Tosylate | bioavailable | cancer | damage | poly ADP ribose polymerase | breast | MK 4827 Tosylate | Inhibitor | MK-4827 | anti-tumor | orally | ovarian | MK4827 Tosylate | MK 4827 | lung | Niraparib | DNA | Niraparib (MK-4827) Tosylate |
| 相关产品 | Stavudine | 5-Fluorouracil | Acetylcysteine | Myricetin | Sodium 4-phenylbutyrate | L-Ascorbic acid | Dextran sulfate sodium salt (MW 4500-5500) | Metronidazole | Sorafenib | Tributyrin |
| 相关库 | 经典已知活性库 | 抗癌临床化合物库 | 药物功能重定位化合物库 | 抑制剂库 | FDA 上市药物库 | 抗癌上市药物库 | 抗衰老化合物库 | 已知活性化合物库 | 抗癌活性化合物库 | 抗癌药物库 |
United States
