4DIJ

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

4DIJ の概要

• エントリーDOI: 10.2210/pdb4dij/pdb
• 関連するPDBエントリー: 1YCR
• 分子名称: 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)
• 機能のキーワード: ppi with p53, ppi inhibitor, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus, nucleoplasm: Q00987
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23493.02

構造登録者

Kallen, J. (登録日: 2012-01-31, 公開日: 2012-05-02, 最終更新日: 2024-04-03)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.9 Å)