| 产品描述： | PARP抑制剂;PARP Inhibitors;;InformationNVP-TNKS656 NVP-TNKS656 is a highly potent, selective, and orally active tankyrase inhibitor with IC50 of 6 nM for TNKS2, > 300-fold selectivity against PARP1 and PARP2.TargetsTNKS2 (Cell-free assay) 6 nMIn vitroNVP-TNKS656 shows low to moderate microsomal ER values across species and high solubility. In PI3K or AKT inhibitor-resistant cells, NVP-TNKS656 blocks Wnt/β-Catenin pathway and promotes apoptosis.In vivoIn mice, NVP-TNKS656 displays low clearance and volume of distribution, and exhibits good exposure and moderate oral bioavailability. In MMTV-Wnt1 tumor bearing athymic nude mice, NVP-TNKS656 (350 mg/kg, p.o.) stabilizes Axin1 protein and reduces the Wnt/beta-catenin target gene Axin2 mRNA level by 70-80%. In colorectal cancer PDX models, NVP-TNKS656 reduces nuclear β-catenin, reverts such resistance, and represses tumor growth. |
| 体内研究： |
NVP-TNKS656 (30 或 100 mg/kg，口服) 表现出良好的暴露和适度的口服生物利用度，分别为 32% 和 53%。在 30 和 100 mg/kg 之间观察到口服暴露的一些轻微超比例增加，其中 100 mg/kg 剂量的剂量标准化 AUC 比 30 mg/kg 剂量高 2 倍。用 NVP-TNKS656 (350 mg/kg，po) 处理的小鼠表现出良好的血浆和肿瘤暴露，对应于 AUC0-24h 分别为 515 和 325 μM·h。 |
| 参考文献： |
1. Shultz MD, et al. Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor. J Med Chem. 2013 Aug 22;56(16):6495-511. |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.022 ml |
10.11 ml |
20.219 ml |
| 5 mM |
0.404 ml |
2.022 ml |
4.044 ml |
| 10 mM |
0.202 ml |
1.011 ml |
2.022 ml |
| 50 mM |
0.04 ml |
0.202 ml |
0.404 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京