title: Design and development of BACE-1 inhibitors.
abstract: In early 1999, beta-amyloid cleaving enzyme-1 (BACE-1) was identified as the protease responsible for the critical first step in the processing of beta-amyloid precursor protein that ultimately leads to the production of Abeta peptides in the brain. Accumulation of these peptides has been implicated in the pathology of Alzheimer's disease (AD). An inhibitor of BACE-1 would therefore have therapeutic potential to slow or halt the progression of this debilitating and ultimately fatal disease. This review provides a perspective on the recent developments in the design of BACE-1 inhibitors. An overview of early research is also included, with particular emphasis on a comprehensive survey of the patent literature.
authors.affiliation: Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jared.cumming@spcorp.com
authors.forename: Jared N
authors.initials: JN
authors.lastname: Cumming
authors.forename: Ulrich
authors.initials: U
authors.lastname: Iserloh
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Kennedy
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004345:Drug Industry / Q000379:methods; D010450:Endopeptidases; D006801:Humans; D015394:Molecular Structure
chemical_list: D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human