4OQ3
Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction
Summary for 4OQ3
| Entry DOI | 10.2210/pdb4oq3/pdb |
| Related | 4DIJ |
| Descriptor | E3 ubiquitin-protein ligase Mdm2, 1-(5-chloro-2-methylphenyl)-5-(3-chlorophenyl)-2-(3-methylphenyl)-1H-imidazole-4-carboxylic acid (3 entities in total) |
| Functional Keywords | ppi with p53, inhibitor complex, ligase-ligase inhibitor complex, ligase/ligase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus, nucleoplasm: Q00987 |
| Total number of polymer chains | 4 |
| Total formula weight | 46437.30 |
| Authors | Kallen, J. (deposition date: 2014-02-07, release date: 2014-04-23, Last modification date: 2023-09-20) |
| Primary citation | Vaupel, A.,Bold, G.,De Pover, A.,Stachyra-Valat, T.,Hergovich-Lisztwan, J.,Kallen, J.,Masuya, K.,Furet, P. Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction. Bioorg.Med.Chem.Lett., 24:2110-2114, 2014 Cited by PubMed Abstract: Capitalizing on crystal structure information obtained from a previous effort in the search for non peptide inhibitors of the p53-MDM2 interaction, we have discovered another new class of compounds able to disrupt this protein-protein interaction, an important target in oncology drug research. The new inhibitors, based on a tetra-substituted imidazole scaffold, have been optimized to low nanomolar potency in a biochemical assay following a structure-guided approach. An appropriate strategy has allowed us to translate the high biochemical potency in significant anti-proliferative activity on a p53-dependent MDM2 amplified cell line. PubMed: 24704029DOI: 10.1016/j.bmcl.2014.03.039 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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