6VUC

Crystal structure of BRD4 bromodomain 1 with N-methylpyrrolidin-2-one (NMP) derivative 7b (1-methyl-4-(4-(piperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-one)

6VUC の概要

• エントリーDOI: 10.2210/pdb6vuc/pdb
• 分子名称: Bromodomain-containing protein 4, (4R)-1-methyl-4-{4-[(piperidin-1-yl)sulfonyl]phenyl}pyrrolidin-2-one (3 entities in total)
• 機能のキーワード: brd4 bd1, bromodomain, nmp, 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: 15290.60

構造登録者

Ilyichova, O.V.,Scanlon, M.J.,Thompson, P.E. (登録日: 2020-02-14, 公開日: 2020-02-26, 最終更新日: 2023-10-11)

主引用文献

Hilton-Proctor, J.P.,Ilyichova, O.,Zheng, Z.,Jennings, I.G.,Johnstone, R.W.,Shortt, J.,Mountford, S.J.,Scanlon, M.J.,Thompson, P.E.
Substituted 1-methyl-4-phenylpyrrolidin-2-ones - Fragment-based design of N-methylpyrrolidone-derived bromodomain inhibitors.
Eur.J.Med.Chem., 191:112120-112120, 2020

PubMed Abstract: N-Methylpyrrolidone is one of several chemotypes that have been described as a mimetic of acetyl-lysine in the development of bromodomain inhibitors. In this paper, we describe the synthesis of a 4-phenyl substituted analogue - 1-methyl-4-phenylpyrrolidin-2-one - and the use of aryl substitution reactions as a divergent route for derivatives. Ultimately, this has led to structurally complex, chiral compounds with progressively improved affinity as inhibitors of bromodomain-containing protein 4.

PubMed: 32120339
DOI: 10.1016/j.ejmech.2020.112120

実験手法

X-RAY DIFFRACTION (1.55 Å)