| 产品描述： | Nedisertib (M3814, Peposertib, MSC2490484A) 是一种口服可利用的、高效且选择性的 DNA activated protein kinase (DNA-PK) 的抑制剂，其IC50值小于3 nM |
| 靶点： |
DNA-PK(Cell-free assay):3 nM |
| 体外研究： |
M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells leads to an increased number of persistent DSBs |
| 体内研究： |
Inhibition of DNA-PK autophosphorylation in xenograft tumors leads to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiates the antitumor activity of IR and lead to complete tumor regression at nontoxic doses |
| 细胞实验： |
Cell lines: 92 cancer cell lines and resting peripheral blood mononuclear cells (PBMCs) Concentrations: 5 μmol/L–5 nmol/L Incubation Time: 120 h Method: Radiosensitization of 92 cancer cell lines and resting peripheral blood mononuclear cells (PBMCs) by M3814 is performed at Oncolead. Cell viability is determined with 3 Gy IR, M3814 (5 μmol/L–5 nmol/L), and a combination of 3 Gy IR and M3814 (5 μmol/L–5 nmol/L). Treated cells are incubated for 120 hours, fixed, stained with sulforhodamine B, and quantified colorimetrically. |
| 动物实验： |
Animal Models: 7- to 9-week-old female NMRI (nu/nu) mice Dosages: 5 mg/kg, 25 mg/kg, 100 mg/kg Administration: Oral gavage |
| 参考文献： |
1. Thomas Fuchss, et al. WO2014183850A1. 2. Frank T Zenke, et al. Pharmacologic Inhibitor of DNA-PK, M3814, Potentiates Radiotherapy and Regresses Human Tumors in Mouse Models. Mol Cancer Ther. 2020 May;19(5):1091-1101. |
| 溶解性： |
Soluble in DMSO、Ethanol |
| 保存条件： |
2-8℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.075 ml |
10.375 ml |
20.751 ml |
| 5 mM |
0.415 ml |
2.075 ml |
4.15 ml |
| 10 mM |
0.208 ml |
1.038 ml |
2.075 ml |
| 50 mM |
0.042 ml |
0.208 ml |
0.415 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