Discovery of novel non-peptide inhibitors of BACE-1 using virtual high-throughput screening.
A novel series of isatin-based inhibitors of beta-secretase (BACE-1) have been identified using a virtual high-throughput screening approach. Structure-activity relationship studies revealed structural features important for inhibition. Docking studies suggest these inhibitors may bind within the BACE-1 active site through H-bonding interactions involving the catalytic aspartate residues.
Yi Mok
N
N
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.
Chadwick
James
J
Kellett
Katherine A B
KA
Hooper
Nigel M
NM
Johnson
A Peter
AP
Fishwick
Colin W G
CW
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D020134:Catalytic Domain; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D019295:Computational Biology; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D007510:Isatin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007510:Isatin; D053829:Amyloid Precursor Protein Secretases