Structural Basis of the Negative Allosteric Modulation of 5-BDBD at Human P2X4 Receptors

• Published in: Molecular pharmacology Vol. 101; no. 1; pp. 33 - 44
• Main Authors: Bidula, Stefan, Nadzirin, Izzuddin Bin, Cominetti, Marco, Hickey, Harry, Cullum, Sean A., Searcey, Mark, Schmid, Ralf, Fountain, Samuel J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2022
• Subjects: Allosteric Regulation - drug effects; Allosteric Regulation - physiology; Benzodiazepinones - chemistry; Benzodiazepinones - metabolism; Benzodiazepinones - pharmacology; HEK293 Cells; Humans; Molecular Dynamics Simulation; Protein Structure, Secondary; Protein Structure, Tertiary; Purinergic P2X Receptor Antagonists - chemistry; Purinergic P2X Receptor Antagonists - metabolism; Purinergic P2X Receptor Antagonists - pharmacology; Receptors, Purinergic P2X4 - chemistry; Receptors, Purinergic P2X4 - metabolism; DMEM; TNP-ATP; 5-BDBD; MD; TLC; AM; HPLC; HEK

The P2X4 receptor is a ligand-gated ion channel activated by extracellular ATP. P2X4 activity is associated with neuropathic pain, vasodilation, and pulmonary secretion and is therefore of therapeutic interest. The structure-activity relationship of P2X4 antagonists is poorly understood. Here we elu...