Progress toward the discovery and development of efficacious BACE inhibitors.
BACE (beta-site amyloid precursor protein [APP] cleavage enzyme) is a transmembrane aspartyl protease responsible for the first cleavage event in the processing of APP to Abeta peptide. Amyloid plaques composed of Abeta peptides are hypothesized to be the root cause of neuronal cell death in Alzheimer's disease patients. Thus, BACE has become a target of significant interest for pharmaceutical and academic research. The recent literature relating to the discovery and development of efficacious BACE inhibitors is reviewed with particular emphasis on the patent literature.
Durham
Timothy B
TB
Eli Lilly & Co, Lilly Corporate Center, Indianapolis, IN 46285, USA. durhamti@lilly.com
Shepherd
Timothy A
TA
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control; D053829:Amyloid Precursor Protein Secretases / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005021:Ethylamines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D010330:Patents as Topic / Q000706:statistics & numerical data; D010601:Pharmacology, Clinical / Q000379:methods* / Q000639:trends
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D005021:Ethylamines; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human