8DU3

Crystal structure of A2AAR-StaR2-bRIL in complex with compound 21a

8DU3 の概要

• エントリーDOI: 10.2210/pdb8du3/pdb
• 分子名称: Adenosine receptor A2a, soluble cytochrome b562 chimera,Soluble cytochrome b562,Adenosine receptor A2a, (4M)-6-bromo-4-(furan-2-yl)quinazolin-2-amine, CHOLESTEROL, ... (6 entities in total)
• 機能のキーワード: gpcr, lcp, antagonists, alzheimer, parkinson, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57348.96

構造登録者

Shiriaeva, A.,Stauch, B.,Han, G.W.,Cherezov, V. (登録日: 2022-07-26, 公開日: 2022-08-10, 最終更新日: 2024-10-16)

主引用文献

Bolteau, R.,Duroux, R.,Laversin, A.,Vreulz, B.,Shiriaeva, A.,Stauch, B.,Han, G.W.,Cherezov, V.,Renault, N.,Barczyk, A.,Ravez, S.,Coevoet, M.,Melnyk, P.,Liberelle, M.,Yous, S.
High ligand efficiency quinazoline compounds as novel A 2A adenosine receptor antagonists.
Eur.J.Med.Chem., 241:114620-114620, 2022

PubMed Abstract: The past fifty years have been marked by the surge of neurodegenerative diseases. Unfortunately, current treatments are only symptomatic. Hence, the search for new and innovative therapeutic targets for curative treatments becomes a major challenge. Among these targets, the adenosine A receptor (AAR) has been the subject of much research in recent years. In this paper, we report the design, synthesis and pharmacological analysis of quinazoline derivatives as AAR antagonists with high ligand efficiency. This class of molecules has been discovered by a virtual screening and bears no structural semblance with reference antagonist ZM-241385. More precisely, we identified a series of 2-aminoquinazoline as promising AAR antagonists. Among them, one compound showed a high affinity towards AAR (21a, K = 20 nM). We crystallized this ligand in complex with AAR, confirming one of our predicted docking poses and opening up possibilities for further optimization to derive selective ligands for specific adenosine receptor subtypes.

PubMed: 35933788
DOI: 10.1016/j.ejmech.2022.114620

実験手法

X-RAY DIFFRACTION (2.5 Å)