9KPI

Aromatic acetyl piperidine derivatives as soluble epoxide hydrolase inhibitor

これはPDB形式変換不可エントリーです。

9KPI の概要

• エントリーDOI: 10.2210/pdb9kpi/pdb
• 分子名称: Bifunctional epoxide hydrolase 2, 1-[1-[2-(3,5-dimethoxyphenyl)ethanoyl]piperidin-4-yl]-3-[[4-(trifluoromethyloxy)phenyl]methyl]urea, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: seh, inhibition, complex, hydrolase
• 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: 63300.38

構造登録者

Wang, H.,Feng, Y.,Du, X.Y. (登録日: 2024-11-22, 公開日: 2025-04-16, 最終更新日: 2025-10-01)

主引用文献

Ding, J.,Zhu, M.Z.,Du, X.Y.,Liu, S.M.,Wang, H.,Liu, X.Z.,Xie, W.S.,Ma, H.L.,Feng, Y.,Zhu, X.H.,Liang, J.H.
Discovery of Phenylacylpiperidine as Novel sEH Inhibitors through Scaffold Hopping of Natural Stilbene.
J.Med.Chem., 68:8980-9013, 2025

PubMed Abstract: Despite the development of soluble epoxide hydrolase (sEH) inhibitors as a promising therapeutic approach, no drug candidate has successfully progressed beyond clinical phase II, highlighting the need for a novel chemotype with improved in vivo potency, pharmacokinetics and safety. In this study, we discovered a phenylacetylpiperidine-based compound, (lab code: ; IC: 0.51 nM), through strategic scaffold hopping from previously reported styrene-based sEH inhibitors. Resolving the cocrystal structure and mode-of-action studies revealed a distinct profile compared to well-known sEH inhibitors and (IC: 44, 19 nM). Notably, demonstrated additional interactions with sEH compared to , and uniquely enhanced anti-inflammatory factors, including EET levels and IL-10, a capability not observed with . Moreover, showed excellent pharmacokinetics and safety, positioning it as a promising candidate for treating both acute and chronic inflammatory diseases, including rheumatoid arthritis, leveraging phenylacylpiperidine scaffolds in sEH-targeted therapies.

PubMed: 40227865
DOI: 10.1021/acs.jmedchem.5c00685

実験手法

X-RAY DIFFRACTION (2.4 Å)