Recent progress in the drug discovery of non-peptidic BACE1 inhibitors

Abstract

Background: β-Secretase, also called BACE1, is a promising molecular target for developing anti-Alzheimer's disease drugs. Several approaches of drug discovery for this therapy have been attempted, for example, substrate-based and structure-based designs, high-throughput screening, fragment-based lead generation and in silico screening. Method: In this review, we describe the design of non-peptidic BACE1 inhibitors from a historical perspective and not by the inhibitor's category. Conclusion: The respective methods have both merits and demerits and should be used in a mutually complementary manner.

Keywords::

• Alzheimer's disease
• BACE1
• BACE1 inhibitor
• fragment-based design
• structure-based design
• β-secretase

Acknowledgements

We thank D Sarma and J-T Nguyen for their help in preparing the manuscript.

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