Fig. 5

NOTCH1 signaling pathway and drug targets. ADAM: metalloproteinase/disintegrin/cysteine-rich; NRR: negative regulatory region; SERCA: Sarco/Endoplasmic Reticulum Calcium-ATPase; LNR: lymph node ratio; HD: heterodimerization domain; SAHM1: hydrocarbon-stapled synthetic peptide stapled α-helical peptide derived from mastermind-like 1 prevent the formation of MAML: co-activator (Mastermind-like-1); ICN1: intracellular domains of NOTCH1;PEST: peptide sequence is rich in proline (P), glutamic acid (E), serine (S), and threonine (T), CSL: transcription factor. ADAM inhibitors inhibit ADAM protease S2 site uptake; γ-secretase inhibitors (GSIs) prevent the cleavage of S3 site of γ-secretase; Monoclonal antibody prevent the change the spatial arrangement of the negative regulatory region (NRR) from exposing the S2 and S3 cleavage sites; SERCA inhibitors include Ca²⁺ ATPase inhibitors prevent transportation of NOTCH1 and the formation of heterodimerization domain (HD); SAHM1 hinder the binding complex of ICN1–CSL–MAML