Abstract
We describe the development of cell-permeable beta-secretase inhibitors that demonstratively inhibit the production of the secreted amino terminal fragment of an artificial amyloid precursor protein in cell culture. In addition to potent inhibition in a cell-based assay (IC50 < 100 nM), these inhibitors display impressive selectivity against other biologically relevant aspartyl proteases.
MeSH terms
-
Amyloid Precursor Protein Secretases
-
Aspartic Acid Endopeptidases / antagonists & inhibitors*
-
Aspartic Acid Endopeptidases / chemistry
-
Binding Sites
-
Cell Line
-
Cell Membrane Permeability
-
Crystallography, X-Ray
-
Drug Design
-
Ethylamines / chemical synthesis*
-
Ethylamines / chemistry
-
Ethylamines / pharmacology
-
Humans
-
Models, Molecular
-
Structure-Activity Relationship
-
Sulfonamides / chemical synthesis*
-
Sulfonamides / chemistry
-
Sulfonamides / pharmacology
Substances
-
Ethylamines
-
Sulfonamides
-
Amyloid Precursor Protein Secretases
-
Aspartic Acid Endopeptidases