Description
γ-
Secretase is a multi-
subunit aspartyl protease that regulates signaling pathways by proteolytically cleaving substrates, abrogating or releasing signaling molecules. One well-
known substrate of this enzyme is Notch, a transmembrane receptor that plays a key role in cell fate decisions including cell proliferation, differentiation, and apoptosis. LY411575 is a cell-
permeable γ-
secretase inhibitor (IC
50 = 0.14 nM) that has been shown to block Notch activation
in vitro at 500 μM. LY411575 can induce apoptosis in Kaposi’s sarcoma cells as well as promote intestinal goblet cell differentiation in a mouse model of colitis. It has also been observed to promote neural differentiation of mouse embryonic stem cells.
Uses
LY-411575 has been used as a potent γ-secretase inhibitor and Notch inhibitor.
Definition
ChEBI: A dibenzoazepine that is 5,7-dihydro-6H-dibenzo[b,d]azepin-6-one which is substituted at the 7 pro-S position by the C-terminal carboxamide nitrogen of N
/element>2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyacetyl]-L-alaninamide. It is a potent, cell permeable and selective gamma-secretase inhibitor. It has been tested as a possible treatment
for Alzheimer's disease and shows promise for its potential to counteract severe hearing loss.
Biochem/physiol Actions
LY-411575 is potent, cell permeable and selective γ-secretase inhibitor that reduces Aβ/42 after acute or chronic treatment, and blocks Notch activation. Studies (Cancer Cell) have shown that treatment with LSN-411575 arrests KrasG12V-driven NSCLCs in association with inhibition of HES1 expression and ERK phosphorylation.
