Structure and modeling in the design of β‐ and γ‐secretase inhibitors
M. Katharine Holloway, Peter A. Hunt, Georgia B. McGaughey · Drug Development Research · 2009
Abstract This review discusses the involvement of structure and modeling in the design of β‐secretase (BACE‐1) and γ‐secretase inhibitors as putative Alzheimer's Disease therapeutics. The early and broad availability of structural information for BACE‐1, a membrane‐tethered aspartyl protease, has led to the use of in silico methods in the overall design and optimization process. However, for γ‐secretase, an integral membrane protein, the lack of a detailed 3D structure has limited the application of computational methods. Drug Dev Res 70, 2009. © 2009 Wiley‐Liss, Inc.