Notch 1 inhibitor

Notch signal is closely related to survival, growth and differentiation of many kinds of cells and individual development in parallel with cytokine/tyrosine kinases, Wnt, TGF-β family/Smad Hedgehog and integrin. On the other hand, abnormal activation of Notch signal has been clarified to be relevant to tumorigenesis and growth of cancer cells.

Interprotein started a discovery research of Notch inhibitor aiming for development of a novel class of anti-cancer agent. Of 4 subclasses of Notch1 to 4, Interprotein selected Notch1 to avoid severe adverse event such as intestinal tract injury-related diarrhea and set it as a target of molecular design of inhibitors.

Notch1 is a receptor expressed on cell surface and its intracellular domain, NICD (RAMANK), forms a stable complex (hetero trimer) with RBP-Jk and MAML-1 in nucleus. Interprotein designed compounds that would inhibit formation of the complex.