Name
Title | ||
|---|---|---|
Discovery of Novel Cathepsin S Inhibitors by Pharmacophore-Based Virtual High-Throughput Screening. |
Abstract | ||
|---|---|---|
The cysteine protease cathepsin S (CatS) is involved in the pathogenesis of autoimmune disorders, atherosclerosis, and obesity. Therefore, it represents a promising pharmacological target for drug development. We generated ligand-based and structure-based pharmacophore models for noncovalent and covalent CatS inhibitors to perform virtual high-throughput screening of chemical databases in order to discover novel scaffolds for CatS inhibitors. An in vitro evaluation of the resulting 15 structures revealed seven CatS inhibitors with kinetic constants in the low micromolar range. These compounds can be subjected to further chemical modifications to obtain drugs for the treatment of autoimmune disorders and atherosclerosis. |
Year | DOI | Venue |
|---|---|---|
2008 | 10.1021/ci800101j | JOURNAL OF CHEMICAL INFORMATION AND MODELING |
Keywords | Field | DocType |
high throughput screening | Pharmacophore,High-throughput screening,CATS,Drug development,In vitro,Combinatorial chemistry,Chemistry,Cathepsin S,Bioinformatics,Cysteine protease | Journal |
Volume | Issue | ISSN |
48 | 8 | 1549-9596 |
Citations | PageRank | References |
2 | 0.42 | 5 |
Authors | ||
12 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Patrick Markt | 1 | 118 | 7.68 |
| Caroline McGoohan | 2 | 2 | 0.42 |
| Brian Walker | 3 | 2 | 0.42 |
| Johannes Kirchmair | 4 | 216 | 42.23 |
| Clemens Feldmann | 5 | 2 | 0.42 |
| Gabriella De Martino | 6 | 2 | 0.42 |
| Gudrun Spitzer | 7 | 59 | 4.76 |
| Simona Distinto | 8 | 99 | 5.17 |
| Daniela Schuster | 9 | 83 | 15.99 |
| Gerhard Wolber | 10 | 271 | 46.07 |
| Christian Laggner | 11 | 104 | 44.31 |
| Thierry Langer | 12 | 257 | 51.63 |