Peptides for specific inhibition of Jag 1-Notch 1 pathway

Abstract

Aberrant cross talk between Notch ligand (e.g. Jag1) and Notch receptor (e.g. Notch1) has been implicated in tumorigenesis in the colon. Inhibition of Notch pathway is therefore an attractive approach for treating diseases with upregulated Jag1 e.g. colorectal cancer (CRC). Pan-notch inhibitors like gamma secretase inhibitors (GSIs) have been developed to inhibit Notch and its downstream events. However, severe gastrointestinal toxicity profiles impede the clinical development of GSIs. The present invention develops novel oligopeptides that specifically inhibit Jag1-Notch1 pathway without interfering DLL1-Notch1 or DLL4-Notch1, which demonstrates a clear advantage over pan-notch inhibitors.