Does anyone have any experience of how to pharmacologically inhibit Notch signaling in vivo? I am working on mouse models of breast cancer, and would like to block Notch1-mediated signaling in the tumors to investigate various endpoints upon treatment. I understand there are the following issues:

1. Inhibiting Notch may have off-target effects, since many of the Notch inhibitors out there target also other molecules.

2. Notch is regulating a plethora of processes throughout the body, in many other tissues and organs, so systemic administration of Notch may have grave side-effects to normal physiology of the mouse.

That being said, does anyone have good experience with regards to which inhibitors work with the best possible result (blocking Notch1 in tumors), while at the same time do not have extreme side- and off-target effects!

Any specific recommendation for an inhibitor/decoy receptor/antagonist etc that has been tested by someone with good results would be tremendously appreciated!