4ERE

crystal structure of MDM2 (17-111) in complex with compound 23

4ERE の概要

• エントリーDOI: 10.2210/pdb4ere/pdb
• 関連するPDBエントリー: 4ERF
• 分子名称: E3 ubiquitin-protein ligase Mdm2, [(3R,5R,6S)-1-[(2S)-1-tert-butoxy-1-oxobutan-2-yl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-3-yl]acetic acid, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: mdm2, p53, protein-protein interaction, 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: 23449.06

構造登録者

Huang, X. (登録日: 2012-04-20, 公開日: 2012-05-23, 最終更新日: 2024-02-28)

主引用文献

Rew, Y.,Sun, D.,Gonzalez-Lopez De Turiso, F.,Bartberger, M.D.,Beck, H.P.,Canon, J.,Chen, A.,Chow, D.,Deignan, J.,Fox, B.M.,Gustin, D.,Huang, X.,Jiang, M.,Jiao, X.,Jin, L.,Kayser, F.,Kopecky, D.J.,Li, Y.,Lo, M.C.,Long, A.M.,Michelsen, K.,Oliner, J.D.,Osgood, T.,Ragains, M.,Saiki, A.Y.,Schneider, S.,Toteva, M.,Yakowec, P.,Yan, X.,Ye, Q.,Yu, D.,Zhao, X.,Zhou, J.,Medina, J.C.,Olson, S.H.
Structure-based design of novel inhibitors of the MDM2-p53 interaction.
J.Med.Chem., 55:4936-4954, 2012

PubMed Abstract: Structure-based rational design led to the discovery of novel inhibitors of the MDM2-p53 protein-protein interaction. The affinity of these compounds for MDM2 was improved through conformational control of both the piperidinone ring and the appended N-alkyl substituent. Optimization afforded 29 (AM-8553), a potent and selective MDM2 inhibitor with excellent pharmacokinetic properties and in vivo efficacy.

PubMed: 22524527
DOI: 10.1021/jm300354j

実験手法

X-RAY DIFFRACTION (1.8 Å)