SRRT (Serrate) Inhibitors

Serrate (SRRT) is a transmembrane protein primarily recognized for its pivotal role within the Notch signaling pathway, an evolutionarily conserved cellular communication system with profound implications in developmental processes and tissue homeostasis. SRRT serves as a ligand for Notch receptors, facilitating intercellular interactions that govern a wide array of cellular decisions. Structurally, SRRT belongs to the Delta/Serrate/LAG-2 (DSL) family of proteins, characterized by an extracellular domain featuring EGF-like repeats and a DSL motif crucial for receptor binding. Upon binding to Notch receptors, SRRT initiates a series of proteolytic cleavages, eventually leading to the release of the Notch intracellular domain (NICD). NICD translocates to the nucleus, where it forms a transcriptional activation complex, modulating the expression of target genes that regulate cell fate determination, proliferation, and differentiation.

SRRT (Serrate) Inhibitor encompasses a group of small molecules designed to modulate SRRT activity within the Notch signaling pathway. These inhibitors operate through various mechanisms, with some directly targeting SRRT, while others affect downstream components or regulators of the pathway. One prominent example is DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester), a well-established γ-secretase inhibitor that indirectly influences SRRT by the cleavage of Notch receptors, including Serrate. By impeding this critical proteolytic step, DAPT effectively halts the transmission of Notch signals mediated by SRRT, thereby modulating key cellular processes. Additionally, other molecules, such as those inhibiting PI3K, MAPK/ERK, or HDACs, indirectly affect SRRT function by targeting pathways that interact with Notch signaling, contributing to the intricate regulation of SRRT-mediated cellular decisions.