avagacestat

Avagacestat is an investigational small molecule drug developed as a selective oral gamma-secretase inhibitor, primarily targeting the production of amyloid beta (Aβ) peptides implicated in Alzheimer’s disease pathology. Unlike earlier gamma-secretase inhibitors, avagacestat was designed to preferentially inhibit the cleavage of amyloid precursor protein (APP) over Notch substrates, aiming to reduce Aβ synthesis while minimizing Notch-related toxicities. Preclinical and clinical studies demonstrated that avagacestat could lower brain Aβ levels with less impact on Notch signaling compared to previous compounds. However, clinical trials in patients with mild to moderate and prodromal Alzheimer’s disease revealed limited efficacy and notable side effects—including gastrointestinal disturbances, dermatologic reactions (such as nonmelanoma skin cancers), and cognitive worsening at higher doses. As a result of these findings, development for Alzheimer’s disease was terminated after Phase 2 trials[1][2][5][6].

Other names

1146699-66-2