4X6X

Human soluble epoxide hydrolase in complex with a three substituted cyclopropane derivative

4X6X の概要

• エントリーDOI: 10.2210/pdb4x6x/pdb
• 関連するPDBエントリー: 4X6Y
• 分子名称: Bifunctional epoxide hydrolase 2, 3-{4-[(1-{[(1s,2R,3S)-2,3-diphenylcyclopropyl]carbamoyl}piperidin-4-yl)oxy]phenyl}propanoic acid (3 entities in total)
• 機能のキーワード: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78262.02

構造登録者

Chiyo, N.,Takai, K.,Ishii, T. (登録日: 2014-12-09, 公開日: 2015-04-08, 最終更新日: 2023-11-08)

主引用文献

Takai, K.,Chiyo, N.,Nakajima, T.,Nariai, T.,Ishikawa, C.,Nakatani, S.,Ikeno, A.,Yamamoto, S.,Sone, T.
Three-dimensional rational approach to the discovery of potent substituted cyclopropyl urea soluble epoxide hydrolase inhibitors.
Bioorg.Med.Chem.Lett., 25:1705-1708, 2015

PubMed Abstract: We have previously reported a series of cyclopropyl urea derivatives as potent orally available soluble epoxide hydrolase (sEH) inhibitors. Here, we designed and synthesized three substituted cyclopropane derivatives that occupy all available pockets of sEH catalytic domain. Compound 14 with a diphenyl substituted cyclopropyl moiety showed good sEH inhibitory activity. Co-crystal structure of this compound and human sEH hydrolase catalytic domain revealed enzyme pockets occupied by the phenoxypiperidine part and the diphenyl cyclopropyl moiety. Furthermore, investigation of the phenoxypiperidine part of compound 14 resulted in the discovery of compound 19, which showed potent sEH inhibitory activity (sub-nM sEH IC50 values).

PubMed: 25800114
DOI: 10.1016/j.bmcl.2015.02.076

実験手法

X-RAY DIFFRACTION (1.8 Å)