Name
Title | ||
|---|---|---|
Discovery of Novel Inhibitors Targeting the Menin-Mixed Lineage Leukemia Interface Using Pharmacophore- and Docking-Based Virtual Screening. |
Abstract | ||
|---|---|---|
Disrupting the interaction between mixed lineage leukemia (MLL) fusion protein and menin provides a therapeutic approach for MLL-mediated leukemia. Here, we aim to discover novel inhibitors targeting the menin-MLL interface with virtual screening. Both structure-based molecular docking and ligand-based pharmacophore models were established, and the models used for compound screening show a remarkable ability to retrieve known active ligands from decoy molecules. Verified by a fluorescence polarization assay, five hits with novel scaffolds were identified. Among them, DCZ_M123 exhibited potent inhibitory activity with an IC50 of 4.71 +/- 0.12 mu M and a K-D of 14.70 +/- 2.13 mu M, and it can effectively inhibit the human MLL-rearranged leukemia cells MV4;11 and KOPN8 with GI(50) values of 0.84 mu M and 0.54 mu M, respectively. |
Year | DOI | Venue |
|---|---|---|
2016 | 10.1021/acs.jcim.6b00185 | JOURNAL OF CHEMICAL INFORMATION AND MODELING |
Field | DocType | Volume |
Myeloid-Lymphoid Leukemia Protein,Leukemia,Pharmacophore,Docking (molecular),Fusion protein,Docking (dog),Combinatorial chemistry,Chemistry,Molecular Docking Simulation,Bioinformatics,Virtual screening | Journal | 56 |
Issue | ISSN | Citations |
9 | 1549-9596 | 0 |
PageRank | References | Authors |
0.34 | 3 | 13 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Yuan Xu | 1 | 0 | 0.34 |
| Liyan Yue | 2 | 0 | 0.34 |
| Yulan Wang | 3 | 0 | 0.34 |
| Jing Xing | 4 | 4 | 1.39 |
| Zhifeng Chen | 5 | 0 | 0.34 |
| Zhe Shi | 6 | 0 | 0.34 |
| Rongfeng Liu | 7 | 1 | 0.69 |
| Yu-Chih Liu | 8 | 1 | 0.69 |
| Xiaomin Luo | 9 | 158 | 15.28 |
| Hualiang Jiang | 10 | 306 | 25.98 |
| Kaixian Chen | 11 | 136 | 12.69 |
| Cheng Luo | 12 | 29 | 7.86 |
| Mingyue Zheng | 13 | 78 | 11.14 |