Identification of New Human P2X7 Antagonists Using Ligand- and Structure-Based Virtual Screening.

ABSTRACT: P2X7 receptors, a subtype of ATP-gated cation channel, have gained attention due to their involvement in inflammatory and neurodegenerative diseases, chronic pain, and cancer. However, despite extensive medicinal chemistry efforts, no P2X7 antagonists have reached clinical approval due to suboptimal pharmacokinetic properties, poor selectivity, and insufficient efficacy in comparison to placebo controls. To address these challenges, we employed a virtual screening workflow integrating ligand-based and structure-based approaches to identify novel P2X7 allosteric antagonists. A 3D pharmacophore model derived from three known P2X7 antagonists (A740003, A804598, and JNJ47965567) was used to filter four libraries of commercially available compounds (approximately 10,000,000 total). These compou

SUBMITTER: Zuanon M 

PROVIDER: S-EPMC12264943 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature