BACE1 inhibitors:from peptide mimics to small molecules / 国际药学研究杂志

Alzheimer′s disease(AD)is a chronic neurodegenerative disorder. According to the amyloid cascade hypothesis, abnormal accumulation of amyloid peptides(Aβ)in the brain resulting in neuronal toxicity is the main cause of AD. β-secretase1 (BACE1)is a rate-limiting enzyme that hydrolyzesβ-amyloid precursor protein(β-APP)to produce amyloid peptides(Aβ). There?fore,BACE1 has been considered to be an attractive therapeutic target for the treatment of AD. Different structural classes of BACE 1 inhibitors have been designed and developed since BACE1 was cloned and identificated. This review highlights the core scaffold to summarize the evolution of structure-based design of BACE1 inhibitors.