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.

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 hydrolyzes β-amyloid precursor protein(β-APP)to produce amyloid peptides(Aβ). Therefore, BACE1 has been considered to be an attractive therapeutic target for the treatment of AD. Different structural classes of BACE1 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.