Discovery of cell-permeable non-peptide inhibitors of beta-secretase by high-throughput docking and continuum electrostatics calculations
| Title | Discovery of cell-permeable non-peptide inhibitors of beta-secretase by high-throughput docking and continuum electrostatics calculations |
| Publication Type | Journal Article |
| Year of Publication | 2005 |
| Authors | Huang D., Lüthi U., Kolb P., Edler K., Cecchini M., Audetat S., Barberis A., Caflisch A. |
| Journal | Journal of Medicinal Chemistry |
| Volume | 48 |
| Issue | 16 |
| Pagination | 5108-5111 |
| Date Published | 2005 Aug 11 |
| Type of Article | Research Article |
| Keywords | Amyloid Precursor Protein Secretases, Animals, Aspartic Acid Endopeptidases, Binding Sites, Carbanilides, Cell Line, Cell Membrane Permeability, Databases, Factual, Endopeptidases, Fluorescence Resonance Energy Transfer, Mammals, Models, Molecular, Phenylurea Compounds, Static Electricity, Structure-Activity Relationship, Thiadiazoles |
| Abstract | A fragment-based docking procedure followed by substructure search were used to identify active-site β-secretase inhibitors from a composite set of about 300 000 and a library of nearly 180 000 small molecules, respectively. EC50 values less than 10 μM were measured in at least one of two different mammalian cell-based assays for 12 of the 72 purchased compounds. In particular, the phenylureathiadiazole 2 and the diphenylurea derivative 3 are promising lead compounds for β-secretase inhibition. |
| DOI | 10.1021/jm050499d |
| pubindex | 0067 |
| Alternate Journal | J. Med. Chem. |
| PubMed ID | 16078830 |
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