Memapsin 2 (Beta-Secretase) Inhibitor Drug, between Fantasy and Reality

Arun   K.   Ghosh; Geoffrey      Bilcer; Lin      Hong; Gerald      Koelsch; Jordan      Tang

Abstract

A major strategy for the development of a disease-modifying therapy against Alzheimers disease is pharmacological intervention designed to reduce levels of β-amyloid in the brain. Among various ways of reducing β-amyloid production, the inhibition of β-secretase (memapsin 2, BACE) is particularly attractive. Not only does β-secretase initiates the amyloid cascade, it also is an aspartic protease, a class of proteases for which successful inhibitor drugs have been developed to treat AIDS patients. Extensive efforts in research and development of a β-secretase inhibitor drug have taken place in many laboratories during the past few years. However, no drug candidate is currently in clinical trials. In spite of the lack of obvious success, much progress has been made to incorporate the drug-like properties in the evolution of better inhibitors. The inhibitors from more recent generations are indeed similar in characteristics to other protease inhibitor drugs. This progress permits optimism that development of clinical candidates of β-secretase inhibitor drugs is a realistic goal.

Keywords: β-secretase, memapsin 2, BACE inhibitor

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