Druggable site near the upper vestibule determines the high affinity and P2X3 homotrimer selectivity of Sivopixant/S-600918 and its analogue DDTPA.

Thus, from the receptor-ligand recognition perspective, we have elucidated the molecular underpinnings of novel RCC clinical candidates' cough-suppressing properties and reduced side effects, offering a promising avenue for the discovery of novel drugs that specifically target P2X3.