P2RX7

P2RX7 (P2X purinoceptor 7), also known as P2X7 receptor, is an ATP-gated cation channel highly expressed in immune cells, neurons, and epithelial tissues. Upon activation by extracellular ATP, it facilitates Na⁺/K⁺ flux and triggers Ca²⁺ influx, promoting pro-inflammatory responses. Sustained activation induces formation of a non-selective pore linked to caspase-1-mediated pyroptosis via NLRP3 inflammasome activation, driving IL-1β and IL-18 release. This receptor is implicated in chronic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease), neurodegenerative disorders (Alzheimer's disease), and tumor microenvironment modulation. Over a dozen P2RX7 antagonists have entered clinical trials, including AZD9056 and JNJ-54175446, though challenges persist in balancing target specificity and blood-brain barrier penetration. Recent focus includes its role in neuropathic pain and dual-target inhibitors for oncology applications.