Semagacestat is a gamma-secretase inhibitor that was developed primarily for the treatment of Alzheimer’s disease. It works by blocking the activity of gamma-secretase, an enzyme involved in the production of amyloid-beta peptides. These peptides accumulate in the brain and form plaques, which are a hallmark of Alzheimer’s pathology. By reducing amyloid-beta production, Semagacestat aimed to slow or halt disease progression. It was evaluated in clinical trials for patients with mild to moderate Alzheimer’s disease. However, studies showed that while it effectively lowered amyloid-beta levels, it did not improve cognitive function and was associated with worsening of symptoms in some patients. Additionally, it caused significant side effects, including skin cancer and infections, likely due to inhibition of gamma-secretase’s role in processing other essential proteins. Due to lack of efficacy and safety concerns, development for Alzheimer’s was discontinued. Despite this, Semagacestat remains a research tool for studying gamma-secretase function and amyloid pathology in neurodegenerative diseases.