Purinergic receptor P2X 7 (P2X7R)

The Purinergic receptor P2X 7 (P2X7R) is an ATP-gated cation channel primarily expressed on immune cells, such as macrophages and microglia [1, 5]. It serves as a key mediator of the inflammatory response by triggering the NLRP3 inflammasome upon activation by high concentrations of extracellular ATP, leading to the maturation and secretion of pro-inflammatory cytokines like IL-1β [1, 10]. Consequently, P2X7R is a significant therapeutic target for chronic inflammatory diseases like rheumatoid arthritis and neuropathic pain [1, 7]. A notable pharmacological challenge associated with certain P2X7 antagonists, such as AZD9056, is their off-target inhibition of the Breast Cancer Resistance Protein (BCRP/ABCG2) transporter [1, 2]. Because BCRP is responsible for the efflux of methotrexate—a standard treatment for rheumatoid arthritis—its inhibition can lead to an indirect drug-drug interaction that increases systemic methotrexate levels and the risk of toxicity [2, 4, 11].

Other names

P2RX7P2X7Purinergic receptor P2X-7ATP receptor

Antagonism of the P2X7 receptor to inhibit ATP-mediated pro-inflammatory cytokine release (e.g., IL-1β) and NLRP3 inflammasome activation [1, 7].