BACE1 inhibitors:A promising therapeutic approach for the management of Alzheimer’s disease  

作　　者：Richa Arya Smita Jain Sarvesh Paliwal Kirtika Madan Swapnil Sharma Achal Mishra Prashant Tiwari Sunil Kumar Kadiri 

机构地区：[1]Banasthali University,Banasthali-304022(Raj.),India [2]Department of Pharmacy,Guru Ghasidas Vishwavidyalaya,Bilaspur,Chhattisgarh-495009,India [3]Department of Pharmacology,College of Pharmaceutical Sciences,Dayananda Sagar University,Bengaluru-560111,India

出　　处：《Asian Pacific Journal of Tropical Biomedicine》2024年第9期369-381,共13页亚太热带生物医学杂志（英文版）

摘　　要：Alzheimer’s disease is a neurological disorder marked by the accumulation of amyloid beta(Aβ)aggregates,resulting from mutations in the amyloid precursor protein.The enzymeβ-secretase,also known asβ-site amyloid precursor protein cleaving enzyme 1(BACE1),plays a crucial role in generating Aβpeptides.With no targeted therapy available for Alzheimer’s disease,inhibiting BACE1 aspartic protease has emerged as a primary treatment target.Since 1999,compounds demonstrating potential binding to the BACE1 receptor have advanced to human trials.Structural optimization of synthetically derived compounds,coupled with computational approaches,has offered valuable insights for developing highly selective leads with drug-like properties.This review highlights pivotal studies on the design and development of BACE1 inhibitors as anti-Alzheimer’s disease agents.It summarizes computational methods employed in facilitating drug discovery for potential BACE1 inhibitors and provides an update on their clinical status,indicating future directions for novel BACE1 inhibitors.The promising clinical results of Elenbecestat(E-2609)catalyze the development of effective,selective BACE1 inhibitors in the future.

关 键 词：BACE1 inhibitors Amyloid precursor protein Β-SECRETASE Structure-based drug design 3D-QSAR β-amyloid precursor protein 

分 类 号：R749.16[医药卫生—神经病学与精神病学]