Insights into binding modes of adenosine A2B antagonists with ligand-based and receptor-based methods

Ligand-based and receptor-based methods were used to investigate the binding modes of human adenosine A2B antagonists. At first, pharmacophore models were developed based on 140 diverse A2B antagonists from literature. Meanwhile, the structural model of A2B receptor was built up based on the crystal structure of human A2A receptor and validated by Induced Fit docking, Glide-XP and Glide-SP docking. Two models matched each other very well and some important implications were hence obtained. The residues of Phe173 and Glu174 in the second extracellular loop and Asn254 were crucial to the antagonists binding to form π–π stacking and hydrogen-bonding interactions. These findings would be very helpful for the discovery of novel and potent A2B antagonists.

Graphical abstractA consensus model of human A2B antagonists was developed. These results provided helpful information for the discovery of novel and potent A2B antagonists.Figure optionsDownload full-size imageDownload as PowerPoint slide