4OQ3

Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction

4OQ3 の概要

• エントリーDOI: 10.2210/pdb4oq3/pdb
• 関連するPDBエントリー: 4DIJ
• 分子名称: 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)
• 機能のキーワード: ppi with p53, inhibitor complex, 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: 4
• 化学式量合計: 46437.30

構造登録者

Kallen, J. (登録日: 2014-02-07, 公開日: 2014-04-23, 最終更新日: 2023-09-20)

主引用文献

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

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: 24704029
DOI: 10.1016/j.bmcl.2014.03.039
主引用文献が同じPDBエントリー

実験手法

X-RAY DIFFRACTION (2.3 Å)