8DU3

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

Summary for 8DU3

• Entry DOI: 10.2210/pdb8du3/pdb
• Descriptor: 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)
• Functional Keywords: gpcr, lcp, antagonists, alzheimer, parkinson, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 57348.96

Authors

Shiriaeva, A.,Stauch, B.,Han, G.W.,Cherezov, V. (deposition date: 2022-07-26, release date: 2022-08-10, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)