7BJ6

Inhibitor of MDM2-p53 Interaction

7BJ6 の概要

• エントリーDOI: 10.2210/pdb7bj6/pdb
• 分子名称: E3 ubiquitin-protein ligase Mdm2, DIMETHYL SULFOXIDE, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: ligase, cell cycle, apoptosis, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12216.97

構造登録者

Williams, P.A. (登録日: 2021-01-14, 公開日: 2021-04-07, 最終更新日: 2024-05-15)

主引用文献

Chessari, G.,Hardcastle, I.R.,Ahn, J.S.,Anil, B.,Anscombe, E.,Bawn, R.H.,Bevan, L.D.,Blackburn, T.J.,Buck, I.,Cano, C.,Carbain, B.,Castro, J.,Cons, B.,Cully, S.J.,Endicott, J.A.,Fazal, L.,Golding, B.T.,Griffin, R.J.,Haggerty, K.,Harnor, S.J.,Hearn, K.,Hobson, S.,Holvey, R.S.,Howard, S.,Jennings, C.E.,Johnson, C.N.,Lunec, J.,Miller, D.C.,Newell, D.R.,Noble, M.E.M.,Reeks, J.,Revill, C.H.,Riedinger, C.,St Denis, J.D.,Tamanini, E.,Thomas, H.,Thompson, N.T.,Vinkovic, M.,Wedge, S.R.,Williams, P.A.,Wilsher, N.E.,Zhang, B.,Zhao, Y.
Structure-Based Design of Potent and Orally Active Isoindolinone Inhibitors of MDM2-p53 Protein-Protein Interaction.
J.Med.Chem., 64:4071-4088, 2021

PubMed Abstract: Inhibition of murine double minute 2 (MDM2)-p53 protein-protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design of novel isoindolinone-based MDM2 inhibitors. MDM2 X-ray crystallography, quantum mechanics ligand-based design, and metabolite identification all contributed toward the discovery of potent and inhibitors of the MDM2-p53 interaction with representative compounds inducing cytostasis in an SJSA-1 osteosarcoma xenograft model following once-daily oral administration.

PubMed: 33761253
DOI: 10.1021/acs.jmedchem.0c02188

実験手法

X-RAY DIFFRACTION (1.59 Å)