Abstract: 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 assubstrates 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 Notch1 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 IC₅₀ values have beenobtained.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.