Fig. 4.

The therapeutic toolkit to modulate Notch signalling. The various strategies to modulate Notch signalling embrace distinct categories of molecules: (i) inhibitors of Notch pre-processing, (ii) molecules uncoupling receptor-ligand interactions including receptor and ligand antibodies and decoys as well as chemical compounds; (iii) inhibitors of NICD formation at the level of the S2 and S3 cleavages, mainly represented by the class of γ-secretase inhibitors (GSIs) and (iv) inhibitors of the trimeric transcriptional complex (RBPJ-MAML1-NICD) assembly. DSL ligands Delta/Serrate/LAG2 ligand, NECD Notch extracellular domain, NEXT Notch extracellular truncation fragment, NTMD Notch transmembrane domain, NICD Notch intracellular domain