8ZHA

HIV-1 integrase core domain in complex with compound 15

これはPDB形式変換不可エントリーです。

8ZHA の概要

• エントリーDOI: 10.2210/pdb8zha/pdb
• 関連するPDBエントリー: 8ZH4
• 分子名称: Integrase, TETRAETHYLENE GLYCOL, (2~{S})-2-[7-(cycloheptylcarbamoyl)-4',5-dimethyl-spiro[1,2-dihydroindene-3,1'-cyclohexane]-4-yl]-2-[(2-methylpropan-2-yl)oxy]ethanoic acid, ... (5 entities in total)
• 機能のキーワード: hiv, integrase, inhibitor, viral protein
• 由来する生物種: Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19433.71

構造登録者

Furuzono, T.,Orita, T.,Nomura, A.,Adachi, T. (登録日: 2024-05-10, 公開日: 2024-07-10, 最終更新日: 2024-10-23)

主引用文献

Adachi, K.,Manabe, T.,Yamasaki, T.,Suma, A.,Orita, T.,Furuzono, T.,Adachi, T.,Ohata, Y.,Akiyama, Y.,Miyazaki, S.
Design and synthesis of novel and potent allosteric HIV-1 integrase inhibitors with a spirocyclic moiety.
Bioorg.Med.Chem.Lett., 110:129864-129864, 2024

PubMed Abstract: We report herein the design and discovery of novel allosteric HIV-1 integrase inhibitors. Our design concept utilized the spirocyclic moiety to restrain the flexibility of the conformation of the lipophilic part of the inhibitor. Compound 5 showed antiviral activity by binding to the nuclear lens epithelium-derived growth factor (LEDGF/p75) binding site of HIV-1 integrase (IN). The introduction of a lipophilic amide substituent into the central benzene ring resulted in a significant increase in antiviral activity against HIV-1 WT X-ray crystallography of compound 15 in complex with the integrase revealed the presence of a hydrogen bond between the oxygen atom of the amide of compound 15 and the hydroxyl group of the T125 side chain. Chiral compound 17 showed high antiviral activity, good bioavailability, and low clearance in rats.

PubMed: 38942126
DOI: 10.1016/j.bmcl.2024.129864

実験手法

X-RAY DIFFRACTION (1.95 Å)