Molecular modeling approaches for the discovery of adenosine A2B receptor antagonists: current status and future perspectives

Adenosine receptors (ARs) are classified as A(1), A(2A),A(2B), and A(3) subtypes belonging to the superfamily of G-protein-coupled receptors (GPCRs). Several molecular modeling approaches have been developed for A(2B)AR and its antagonists, from the construction of a homology model, molecular docking, molecular dynamics (MD) simulations, and 3D quantitative structure-activity relationship (QSAR) modeling to pharmacophore modeling, each of which has different objectives and outcomes. In this review, we provide a systematic outline of advances in molecular modeling approaches towards A(2B)AR for deducing its structure and interactions with various types of antagonist. The information, methods and perspectives presented here provides impetus for medicinal chemists to discover potential ligands that can bind selectively with higher affinity to A(2B)AR.