Boom in the development of non-peptidic beta-secretase (BACE1) inhibitors for the treatment of Alzheimer's disease.
Beta-amyloid cleaving enzyme-1 (BACE1) has become a significant target for the therapy of Alzheimer's disease. After the discovery of the first non-peptidomimetic beta-secretase inhibitors by Takeda Chemicals in 2001, several research teams focused on SAR development of these agents. The non-peptidic BACE1 inhibitors may potentially overcome the classical problems associated with the peptide structure of first generation, such as blood-brain barrier crossing, poor oral bioavailability and susceptibility to P-glycoprotein transport. In the past 6 years a boom in research of non-peptidic BACE1 inhibitors has disseminated findings over hundreds of publications and patents. The rapidly growing literature has been reviewed with particular emphasis on literature of pharmaceutical companies.
Silvestri
Romano
R
Istituto Pasteur, Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Roma, Italy. romano.silvestri@uniroma1.it
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004345:Drug Industry / Q000639:trends; D011480:Protease Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D012106:Research / Q000639:trends; D013329:Structure-Activity Relationship
D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases