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

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.