semagacestat

Semagacestat is a small molecule γ-secretase inhibitor that was developed as an investigational treatment for Alzheimer's disease. Its mechanism of action involves blocking the γ-secretase enzyme, which is responsible for the proteolytic cleavage of amyloid precursor protein (APP) to produce β-amyloid peptides, including Aβ40 and Aβ42—the main constituents of amyloid plaques in Alzheimer's disease. By inhibiting γ-secretase, semagacestat aimed to reduce the formation and secretion of these neurotoxic peptides, thereby targeting a key upstream event in the amyloid cascade hypothesis. The drug was originally developed by Eli Lilly and advanced into Phase 3 clinical trials; however, development was halted after studies showed it failed to slow disease progression and was associated with worsening cognition and daily functioning as well as increased incidence of skin cancer[1][3][4][5].

Other names

semagacestat