4DIJ

The Central Valine Concept Provides an Entry in a New Class of Non Peptide Inhibitors of the P53-MDM2 Interaction

Summary for 4DIJ

• Entry DOI: 10.2210/pdb4dij/pdb
• Related: 1YCR
• Descriptor: E3 ubiquitin-protein ligase Mdm2, 6-chloro-3-[1-(4-chlorobenzyl)-4-phenyl-1H-imidazol-5-yl]-N-[2-(morpholin-4-yl)ethyl]-1H-indole-2-carboxamide (3 entities in total)
• Functional Keywords: ppi with p53, ppi inhibitor, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus, nucleoplasm: Q00987
• Total number of polymer chains: 2
• Total formula weight: 23493.02

Authors

Kallen, J. (deposition date: 2012-01-31, release date: 2012-05-02, Last modification date: 2024-04-03)

Primary citation

Furet, P.,Chene, P.,De Pover, A.,Valat, T.S.,Lisztwan, J.H.,Kallen, J.,Masuya, K.
The central valine concept provides an entry in a new class of non peptide inhibitors of the p53-MDM2 interaction.
Bioorg.Med.Chem.Lett., 22:3498-3502, 2012

PubMed Abstract: Disrupting the interaction between the p53 tumor suppressor and its regulator MDM2 is a promising therapeutic strategy in anticancer drug research. In our search for non peptide inhibitors of this protein-protein interaction, we have devised a ligand design concept exploiting the central position of Val 93 in the p53 binding pocket of MDM2. The design of molecules based on this concept has allowed us to rapidly identify compounds having a 3-imidazolyl indole core structure as the first representatives of a new class of potent inhibitors of the p53-MDM2 interaction.

PubMed: 22507962
DOI: 10.1016/j.bmcl.2012.03.083

Experimental method

X-RAY DIFFRACTION (1.9 Å)