Compounds and methods to target transmembrane domain of membrane proteins (e.g., APPTM) to inhibit intramembrane proteolysis

Intramembrane proteolytic cleavage is an important process in a number of signaling pathways and pathologies. One of the best-known is that of Alzheimer’s Disease (AD), where the gamma-secretase enzyme cleaves amyloid precursor protein (APP) to create free amyloid. This free amyloid accumulates to form amyloid plaques during the later stages of the disease. New drugs are urgently needed to address AD and the disclosed compound represents such potential drug. This technology is a compound that can bind and covalently modify the transmembrane (TM) domain of the amyloid precursor protein.