您好,欢迎来到化工原料网! [登录] [免费注册]
化工原料网
位置:首页 > 产品库 > M3814(nedisertib)
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
M3814(nedisertib)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
M3814(nedisertib)图片
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议

产品介绍

M3814是一个有效且有选择性的DNA依赖性蛋白激酶(DNA-PK)的抑制剂。

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].

产品描述

Nedisertib (M3814) is a potent and selective inhibitor of DNA-dependent Protein Kinase (DNA-PK), with an IC50 of <3 nM.

Nedisertib (Compound 136) is a potent and selective inhibitor of DNA-PK, with an IC50 of <3 nM for DNA-PK and <0.5 μΜ for cellular pDNA-PK[3].

In combination with IR, Nedisertib shows efficacy in all of the 6 mouse models of human cancer. In all models, a dose of 2 Gy administered daily for 1 week in combination with Nedisertib induces statically significant tumor growth inhibition compare to IR alone. Nedisertib, alone or in combination with IR, does not induce significant weight loss or visual signs of toxicity in the mice in any study[1].

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].

Reference:
[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.
[2]. Frank T. Zenke, et al. Abstract 1658: M3814, a novel investigational DNA-PK inhibitor: enhancing the effect of fractionated radiotherapy leading to complete regression of tumors in mice. AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1658.
[3]. Thomas Fuchss, et al. Arylchinazoline. WO2014183850A1.