Jagged1 Inhibitors

Common Jagged1 Inhibitors include, but are not limited to DAPT CAS 208255-80-5, Dibenzazepine (Deshydroxy LY 411575) CAS 209984-56-5, RO-4929097 CAS 847925-91-1, FLI-06 CAS 313967-18-9 and Curcumin CAS 458-37-7.

Jagged1, a member of the Jagged family of transmembrane ligands, is a key component of the Notch signaling pathway, which plays fundamental roles in various cellular processes including development, differentiation, proliferation, and apoptosis. Specifically, Jagged1 functions as a ligand for Notch receptors, facilitating cell-cell communication and triggering downstream signaling events upon binding to Notch receptors on neighboring cells. Activation of the Notch pathway through Jagged1 binding leads to the proteolytic cleavage of the Notch receptor, releasing the intracellular domain of Notch (NICD) that translocates to the nucleus. Within the nucleus, NICD forms a transcriptional complex with other proteins, such as CSL (CBF1/Su(H)/Lag-1), Mastermind-like (MAML), and various co-activators, to regulate the expression of target genes involved in cellular fate determination and tissue homeostasis.

Inhibition of Jagged1-mediated Notch signaling represents a strategy to modulate Notch pathway activity and its downstream effects. One common mechanism of inhibition involves the blockade of Jagged1-Notch receptor interactions, either by disrupting the physical interaction between Jagged1 and Notch receptors or by preventing the activation of Notch receptors upon ligand binding. This can be achieved through the use of blocking antibodies or small molecules that specifically target the Jagged1 ligand or the extracellular domain of Notch receptors. Additionally, inhibitory strategies may also involve targeting downstream components of the Notch signaling pathway, such as γ-secretase inhibitors, which prevent the cleavage of Notch receptors and subsequent release of NICD. By interfering with Jagged1-mediated Notch signaling, inhibition strategies aim to modulate cellular processes controlled by the Notch pathway, offering avenues for diseases associated with dysregulated Notch signaling, including cancer, cardiovascular diseases, and developmental disorders.