NF340

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 cord 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 calcium ²⁺ concentration and cell migration in human hepatocellular carcinoma cells. NF340 is applicable to the research of neuropathic pain, myocardial ischemia/reperfusion injury, inflammatory pain, rheumatoid arthritis and hepatocellular carcinoma^{[1][2][3][4][5]}. IC50 & Target:P2Y11 receptor^[1] In Vitro:NF340 inhibits the P2Y₁₁R-mediated modulation of adult ventricular human CF secretome, abolishing the NF546-induced reduction in human DC maturation marker expression and reducing the NF546-induced protective effect on human cardiomyocyte viability after simulated I/R injury^[2].
NF340 is a selective antagonist of human P2Y11 receptors, with a pEC₅₀ of 7.3-7.7, showing 1000-fold lower potency at other human P2Y receptor subtypes^[3].
NF340 (10-20 μM; 24 h) dose-dependently inhibits IL-1β-induced TNF-α and IL-6 expression at both mRNA and protein levels in human fibroblast-like synoviocytes, with 20 μM NF340 exerting a stronger inhibitory effect than 10 μM NF340^[4].
NF340 (10-20 μM; 24 h) dose-dependently inhibits IL-1β-induced MMP-1, MMP-3, and MMP-13 expression at both mRNA and protein levels in human fibroblast-like synoviocytes, with 20 μM NF340 exerting a stronger inhibitory effect than 10 μM NF340^[4].
NF340 (10-20 μM; 24 h) dose-dependently ameliorates IL-1β-induced oxidative stress in human fibroblast-like synoviocytes, as measured by reduced cellular ROS and 4-HNE levels, with 20 μM NF340 exerting a stronger inhibitory effect than 10 μM NF340^[4].
NF340 (10-20 μM; 6 h (p-IκBα assay); 24 h (nuclear p65 and luciferase assays)) dose-dependently inhibits IL-1β-induced NF-κB activation in human fibroblast-like synoviocytes, as measured by reduced IκBα phosphorylation, nuclear p65 accumulation, and NF-κB promoter activity, with 20 μM NF340 exerting a stronger inhibitory effect than 10 μM NF340^[4].
NF340 (10 μM; 5 min) potently inhibits ATP-induced intracellular calcium elevation in Huh-7 human hepatocellular carcinoma cells^[5].
NF340 (10 μM; 5 min) significantly reduces NF546-induced intracellular calcium elevation in HepG2 human hepatocellular carcinoma cells^[5].
NF340 (10 μM; 24 h) completely blocks ATP-induced migration of Huh-7 human hepatocellular carcinoma cells without affecting basal migration^[5]. In Vivo:NF340 (0.3-30 μM; i.t.; single bolus injection; 6-hour assessment period; 30 μM; i.t.; every 12 hours; 3 days) produces dose-dependent antiallodynic effects in neuropathic rats and reverses spinal nerve injury-induced up-regulation of spinal P2Y₁₁ receptors, indicating spinal P2Y₁₁ receptors participate in maintaining neuropathic pain^[1].
NF340 (1-10 nmol/paw; s.c.; 10 minutes before formalin injection) produces peripherally localized antinociception in the second phase of formalin-induced inflammatory pain in female Wistar rats^[3].
NF340 (1 nmol/paw; s.c.; co-administered with P2Y₁₁ receptor agonists; 10 minutes before formalin injection) blocks P2Y₁₁ agonist-induced pronociception in formalin-induced inflammatory pain in female Wistar rats^[3].