摘要
Notch信号通路与生物体的发育及多种癌症的发生密切相关,目前针对Notch信号通路的药物筛选模型均以鼠源Notch蛋白为底物,未见以人源Notch为底物的报道。本文克隆并表达提纯了人源Notch1截短形式N100,以之为底物首次构建了Notch信号通路体外和细胞的药物筛选模型。同时,用已知Notch通路抑制剂对此模型进行了验证,得到了相应的IC50值。本研究构建的模型能有效应用于人源Notch信号通路的调控剂筛选,为高效发现靶向Notch通路的调控剂奠定了基础。
Notch signal pathway is closely related to the organism＇s development and a variety of cancers. Current models available for screening modulators of Notch signal pathway all use mouse Notch protein as substrates and those models which use human Notch protein have not been reported. To make the screen results much more reliable, the authors cloned a truncated form of human Notch 1 called N100, and built the screening models for the use of it instead of mouse Notch protein. The models included an in vitro screening model based on the purified γ-secretase enzyme and a cell model using luciferase reporter system. The screening models then have been verified by the known modulators of Notch signal pathway and the IC 50 values have been obtained. The verified models can be used to screen modulators of human Notch signaling pathway effectively and it can lay the foundation for finding new modulators of this kind effectively.
出处
《药学学报》
CAS
CSCD
北大核心
2014年第6期837-842,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金面上基金资助项目(31270853)
