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Concept: Adenosine receptors


Methotrexate (MTX) exerts at least part of its anti-inflammatory effects through adenosine receptors (ADOR). The aims of this study were to determine the expression of all four adenosine receptor genes (ADORA1, ADORA2A, ADORA2B, ADORA3 and ADORA3variant) in rheumatoid synovial tissue and any influence of MTX exposure on this expression. Furthermore, we investigated whether polymorphisms within ADORA3 were associated with response and/or adverse effects associated with MTX.

Concepts: Rheumatoid arthritis, Adenosine receptor, Adenosine, Adenosine A2A receptor, Adenosine A1 receptor, Adenosine receptors


Abstract Adenosine receptors have been considered as potential targets for drug development, but one of the main obstacles to this goal is to selectively inhibit one receptor subtype over the others. This subject is particularly crucial for adenosine A2b receptor antagonists (AdoRA2B). The structure–activity relationships of xanthine derivatives which are AdoRA2B have been comprehensively investigated, but the steric and electronic requirements of deazaxanthine AdoRA2B have not been described from a quantitative standpoint of view. Herein we report our efforts to shorten this knowledge gap through 2D-QSAR (HQSAR) and 3D-QSAR (CoMFA) approaches. The good statistical quality (HQSAR - r(2 )= 0.85, [Formula: see text]= 0.77; CoMFA - r(2 )= 0.86, q(2 )= 0.70) and predictive ability ([Formula: see text]= 0.78, [Formula: see text] = 0.78 and [Formula: see text] = 0.70, [Formula: see text] = 0.70, respectively) of the models, along with the information provided by contribution and contour maps hints their usefulness to the design of more potent 9-deazaxanthine derivatives.

Concepts: Receptor, Ligand, Receptor antagonist, Caffeine, Inverse agonist, Adenosine receptor, Adenosine receptors, Adenosine A2B receptor