LY3202626

LY3202626 is a potent, orally available small-molecule inhibitor of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), developed by Eli Lilly for the treatment of Alzheimer's disease. BACE1 is the β-secretase enzyme responsible for cleaving amyloid precursor protein (APP) to generate C99 fragments, which are subsequently processed to form amyloid-beta (Aβ) peptides implicated in Alzheimer’s pathology. By inhibiting BACE1, LY3202626 reduces the production of Aβ peptides and was designed as a maintenance therapy to limit Aβ accumulation after initial plaque clearance by other therapies. The drug demonstrated high potency and central nervous system penetration in preclinical and early clinical studies, with significant reductions in cerebrospinal fluid Aβ levels observed in both animals and humans. Despite promising pharmacodynamic effects and safety profiles in early trials, development was discontinued after Phase 2 due to lack of efficacy on cognitive outcomes[1][2][3][4][7].