P2Y11 Receptor Antagonist

NF340 is a P2Y11 receptor inhibitor with a pIC₅₀ of 7.3-7.7 against human P2Y11 receptor, and it exhibits high selectivity over other P2Y family receptors. NF340 binds to the ATP-binding amino acid residues of the P2Y11 receptor to inhibit its activity, block nociceptive activity, and reduce spinal dorsal horn P2Y11 receptor upregulation induced by spinal nerve injury. NF340 attenuates the NFκB signaling pathway activated by IL-1β by decreasing IκBα phosphorylation, nuclear p65 accumulation, and NFκB promoter activity. NF340 inhibits IL-1β-induced pro-inflammatory cytokine expression, reduces intracellular ROS and 4-HNE levels, and suppresses IL-1β-induced matrix metalloproteinase expression in primary fibroblast-like synoviocytes. NF340 inhibits ATP-induced elevation of intracellular Ca²⁺ concentration and cell migration in human hepatocellular carcinoma cells. NF340 can be used in the research of neuropathic pain, myocardial ischemia/reperfusion injury, inflammatory pain, rheumatoid arthritis, and hepatocellular carcinoma.