7OE4

C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-methyl-4-propionyl-1H-pyrrole-2-carboxamide

これはPDB形式変換不可エントリーです。

7OE4 の概要

• エントリーDOI: 10.2210/pdb7oe4/pdb
• 分子名称: Bromodomain-containing protein 2, 1,2-ETHANEDIOL, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL, ... (5 entities in total)
• 機能のキーワード: inhibitor, bromodomain, nuclear protein
• 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: 14215.37

構造登録者

Chung, C. (登録日: 2021-05-01, 公開日: 2021-07-28, 最終更新日: 2024-05-01)

主引用文献

Seal, J.T.,Atkinson, S.J.,Bamborough, P.,Bassil, A.,Chung, C.W.,Foley, J.,Gordon, L.,Grandi, P.,Gray, J.R.J.,Harrison, L.A.,Kruger, R.G.,Matteo, J.J.,McCabe, M.T.,Messenger, C.,Mitchell, D.,Phillipou, A.,Preston, A.,Prinjha, R.K.,Rianjongdee, F.,Rioja, I.,Taylor, S.,Wall, I.D.,Watson, R.J.,Woolven, J.M.,Wyce, A.,Zhang, X.P.,Demont, E.H.
Fragment-based Scaffold Hopping: Identification of Potent, Selective, and Highly Soluble Bromo and Extra Terminal Domain (BET) Second Bromodomain (BD2) Inhibitors.
J.Med.Chem., 64:10772-10805, 2021

PubMed Abstract: The profound efficacy of pan-BET inhibitors is well documented, but these epigenetic agents have shown pharmacology-driven toxicity in oncology clinical trials. The opportunity to identify inhibitors with an improved safety profile by selective targeting of a subset of the eight bromodomains of the BET family has triggered extensive medicinal chemistry efforts. In this article, we disclose the identification of potent and selective drug-like pan-BD2 inhibitors such as pyrazole (GSK809) and furan (GSK743) that were derived from the pyrrole fragment . We transpose the key learnings from a previous pyridone series (GSK620 as a representative example) to this novel class of inhibitors, which are characterized by significantly improved solubility relative to our previous research.

PubMed: 34255512
DOI: 10.1021/acs.jmedchem.1c00365

実験手法

X-RAY DIFFRACTION (1.653 Å)