Submit Manuscript  

Article Details

Structure-Based Rational Design of Adenosine Receptor Ligands

[ Vol. 17 , Issue. 1 ]


Hugo Gutiérrez-de-Terán, Jessica Sallander and Eddy Sotelo   Pages 40 - 58 ( 19 )


The family of adenosine receptors (ARs) is focus of several medicinal chemistry programs aimed to find new potent and selective drugs. Each receptor subtype has been proposed as a relevant drug target in the treatment of, e.g., cardiovascular or inflammatory diseases, asthma or Parkinson’s disease. Until recently, most of these efforts have been dominated by ligand-based or empirical approaches. However, the latest advances in G protein-coupled receptor (GPCR) crystallography allowed for a thorough structural characterization of the A2AAR subtype, which has been crystalized with a number of agonists and antagonists. Consequently, the ligand discovery of AR ligands has been enriched with a number of structure-based approaches. These include the generation of higher-confident homology models for the remaining AR subtypes, virtual screening identification of novel chemotypes, structure-based lead-optimization programs, rationalization of selectivity profiles, or the structural characterization of novel binding sites that enable the design of novel allosteric modulators. Computational methodologies have importantly contributed to the success of these structure-based approaches, and the recent advances in the field are also analyzed in this review. We conclude that the design of adenosine receptor ligands has improved dramatically with the consideration of structure- based approaches, which is paving the way to a better understanding of the biology and pharmacological modulation of this relevant family of receptors.


Docking, Homology modeling, Free energy of binding, QSAR, Solvation, Selectivity, Virtual screening.


Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.

Graphical Abstract:

Read Full-Text article