5V18

Structure of PHD2 in complex with 1,2,4-Triazolo-[1,5-a]pyridine

5V18 の概要

• エントリーDOI: 10.2210/pdb5v18/pdb
• 関連するPDBエントリー: 5V1B
• 分子名称: Egl nine homolog 1, SULFATE ION, 4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile, ... (5 entities in total)
• 機能のキーワード: hif prolylhydroxylase domain-2, inhibitor, momodentate binding, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q9GZT9
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27161.58

構造登録者

Skene, R.J. (登録日: 2017-03-01, 公開日: 2017-06-21, 最終更新日: 2024-03-06)

主引用文献

Ahmed, S.,Ayscough, A.,Barker, G.R.,Canning, H.E.,Davenport, R.,Downham, R.,Harrison, D.,Jenkins, K.,Kinsella, N.,Livermore, D.G.,Wright, S.,Ivetac, A.D.,Skene, R.,Wilkens, S.J.,Webster, N.A.,Hendrick, A.G.
1,2,4-Triazolo-[1,5-a]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Binding Interaction.
J. Med. Chem., 60:5663-5672, 2017

PubMed Abstract: Herein we describe the identification of 4-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}benzonitrile-based inhibitors of the hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme. These inhibitors were shown to possess a novel binding mode by X-ray crystallography, in which the triazolo N1 atom coordinates in a hitherto unreported monodentate interaction with the active site Fe ion, while the benzonitrile group accepts a hydrogen-bonding interaction from the side chain residue of Asn315. Further optimization led to potent PHD-1 inhibitors with good physicochemical and pharmacokinetic properties.

PubMed: 28594552
DOI: 10.1021/acs.jmedchem.7b00352

実験手法

X-RAY DIFFRACTION (2.15 Å)