Unveiling the Structure-Activity Relationships at the Orthosteric Binding Site of P2X Ion Channels: The Route to Selectivity.

The orthosteric ATP-binding site of the P2X receptors is poorly understood. Only a few compounds were well characterized for their P2X receptor functional activity and subtype selectivity. This study represents the first fully functional characterization of various ATP derivatives combined with in silico studies to advance the understanding of SARs at the orthosteric binding sites of P2X receptors leading to the identification of several subtype-selective P2X receptor agonists and compounds with agonistic as well as antagonistic profiles.