- 首页
- NA-PKcs (DNA-dependent protein kinase, catalytic subunit)
- M3814 (nedisertib)
M3814 (nedisertib)
Nedisertib (M3814, Peposertib, MSC2490484A) is an orally bioavailable, highly potent and selective inhibitor of DNA activated protein kinase (DNA-PK) with IC50 of < 3 nM.
此产品仅用于科学研究，我们不为任何个人用途提供产品和服务
-
包装价格促销价数量
-
5mg￥1832.001648.00- +
-
10mg￥2822.002539.00- +
-
25mg￥5646.005081.00- +
-
50mg￥9114.008202.00- +
-
100mg￥14860.0013374.00- +
- 货号: ajce49678
- CAS: 1637542-33-6
- 别名: M3814
- 分子式: C24H21ClFN5O3
- 分子量: 481.91
- 纯度: ＞98%
- 溶解度: DMSO : 100 mg/mL (207.51 mM);Water : < 0.1 mg/mL (insoluble)
- 储存: Store at -20°C
- 库存: 现货
Background
Nedisertib (M3814, Peposertib, MSC2490484A) is an orally bioavailable, highly potent and selective inhibitor of DNA activated protein kinase (DNA-PK) with IC50 of < 3 nM.
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.[2]
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.[2]
[1] Thomas Fuchss, et al. WO2014183850A1. [2] Frank T Zenke, et al. Mol Cancer Ther. 2020 May;19(5):1091-1101.
Protocol
Animal experiment: | The efficacy of Nedisertib in combination with IR is evaluated in 6 human xenograft models (HCT116, FaDu, NCI-H460, A549, Capan-1, BxPC3) in mice representing 4 different cancer types (colon, head and neck, lung, and pancreas). Tumor cells are injected s.c. into nude mice, and treatment starts when palpable tumors are established (~100 to 200 mm3 ). Nedisertib is given orally at different doses (25 to 300 mg/kg) 10 min prior to IR. IR is applied using a radiation therapy device for small rodents calibrated to deliver 2 Gy. Autophosphorylation of DNA-PK (serine2056 ) in FaDu tumor lysates is measured by immunoassay to assess pharmacological inhibition by Nedisertib[1]. |
参考文献: [1]. L. Damstrup, et al. M3814, a DNA-dependent Protein Kinase Inhibitor (DNA-PKi), Potentiates the Effect of Ionizing Radiation (IR) in Xenotransplanted Tumors in Nude Mice. IJROBP. 2016; 94, 940-941. | |
