Name
Abstract | ||
|---|---|---|
The p53-MDM2 interaction is a well-known protein-protein contact, and its disruption is a key event for p53 activation and induction of its oncosuppressor response. The design of small molecules that can block the p53-MDM2 interaction and reactivate the p53 function is a promising strategy for cancer therapy. To date, several compounds have been identified as p53-MDM2 inhibitors, and X-ray structures of MDM2 complexed with several ligands are available in the Brookhaven Protein Data Bank. These data have been p53-11131112 interaction exploited to compile a hierarchical virtual screening protocol. The first steps were aimed at selecting a focused library, which was submitted in parallel to docking and pharmacophore model alignment. Selected compounds were subjected to inhibition assays of both cellular vitality (MTT) and p53-MDM2 interaction (ELISA and co-immunoprecipitation), disclosing four nanomolar inhibitors. |
Year | DOI | Venue |
|---|---|---|
2016 | 10.1021/acs.jcim.5b00747 | JOURNAL OF CHEMICAL INFORMATION AND MODELING |
Field | DocType | Volume |
Pharmacophore,Docking (dog),Combinatorial chemistry,Molecular Docking Simulation,Mdm2,Chemistry,Small molecule,Structure–activity relationship,Bioinformatics,Virtual screening,Protein Data Bank | Journal | 56 |
Issue | ISSN | Citations |
SP6 | 1549-9596 | 0 |
PageRank | References | Authors |
0.34 | 3 | 10 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Paolo Tortorella | 1 | 0 | 0.34 |
| Antonio Laghezza | 2 | 0 | 0.34 |
| Milena Durante | 3 | 0 | 0.34 |
| Isabel Gomez-Monterrey | 4 | 0 | 0.34 |
| Alessia Bertamino | 5 | 0 | 0.34 |
| Pietro Campiglia | 6 | 0 | 0.34 |
| Fulvio Loiodice | 7 | 0 | 0.68 |
| Simona Daniele | 8 | 1 | 0.68 |
| Claudia Martini | 9 | 1 | 0.68 |
| Mariangela Agamennone | 10 | 0 | 0.34 |