Name
Abstract | ||
|---|---|---|
The discovery of multitarget drugs has recently attracted much attention. Most of the reported multitarget ligands have been serendipitous discoveries. Although a few methods have been developed for rational multitarget drug discovery, there is a lack of elegant methods for de nova multitarget drug design and optimization, especially for multiple targets with large differences in their binding sites. In this paper, we report the first de nova multitarget ligand design method, with an iterative fragment-growing strategy. Using this method, dual-target inhibitors for COX-2 and LTA(4)H were designed, with the most potent one inhibiting PGE(2) and LTB4 production in the human whole blood assay with IC50 values of 7.0 and 7.1 mu M, respectively. Our strategy is generally applicable in rational and efficient multitarget drug design, especially for the design of highly integrated inhibitors for proteins with dissimilar binding pockets. |
Year | DOI | Venue |
|---|---|---|
2014 | 10.1021/ci500021v | JOURNAL OF CHEMICAL INFORMATION AND MODELING |
Field | DocType | Volume |
Drug discovery,Binding site,Ligand,Combinatorial chemistry,Chemistry,Drug | Journal | 54 |
Issue | ISSN | Citations |
4 | 1549-9596 | 3 |
PageRank | References | Authors |
0.38 | 3 | 6 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Erchang Shang | 1 | 3 | 0.38 |
| Yaxia Yuan | 2 | 16 | 1.56 |
| Xinyi Chen | 3 | 3 | 0.38 |
| Ying Liu | 4 | 8 | 0.97 |
| Jianfeng Pei | 5 | 37 | 3.99 |
| Luhua Lai | 6 | 369 | 33.78 |