GPR84 antagonist 2 (compound 33) is a potent, selective, and orally active GPR84 antagonist (IC50=8.95 nM). GPR84 antagonist 2 shows improved potency in the calcium mobilization assay and the ability to inhibit the chemotaxis of neutrophils and macrophages upon GPR84 activation. GPR84 antagonist 2 has the potential for the research of ulcerative colitis[1].
Setogepram (PBI-4050) acts as an orally active agonist for GPR40 and as an antagonist or inverse agonist for GPR84[1]. Setogepram (PBI-4050) decreases renal, liver and pancreatic fibrosis[1][2]. Setogepram (PBI-4050) exerts anti-fibrotic, anti-inflammatory and anti-proliferative actions[2].
GPR84 antagonist 8 is a selective GPR84 antagonist.
A novel potent and selective agonist of GPR84 that induces calcium response with EC50 of 0.213 uM; does not evoke calcium responses in HEK293 cells expressing other FFARs, including GPR40, GPR41, GPR119, and GPR120; increases in intracellular calcium concentrations in HEK293/Gα16/GPR84 cells with EC50 of 1.01 uM; activates several GPR84-mediated signaling pathways, including calcium mobilization, inhibition of cAMP accumulation, phosphorylation of ERK1/2, receptor desensitization and internalization, and receptor-β-arrestin interaction; reduces forskolin-stimulated cAMP accumulation in HEK293 cells with EC50 of 0.134 uM.
6-OAU(GTPL5846; 6-n-octylaminouracil) is a surrogate agonist of GPR84; activates human GPR84 in the presence of Gqi5 chimera in HEK293 cells with an EC50 of 105 nM in the PI assay.IC50 value: 105 nM [1]Target: GPR84 agonistin vitro: 6-OAU increased [35S]GTPγS incorporated in Sf9 cell membranes expressing human GPR84-Gαi fusion protein with an EC50 of 512 nM. 6-OAU did not activate human GPR40 in HEK293 cells in the PI assay. Stimulation with 6.25 μm 6-OAU began to induce GPR84-EGFP internalization, and the extensive internalization was observed at 200 μm 6-OAU stimulation. In a Transwell assay, 3-OH-C12 and the surrogate agonist, 6-OAU, provoked chemotaxis of PMNs prepared from human peripheral blood in a concentration-dependent manner with an EC50 of 24.2 μm and 318 nm, respectively. In addition, 3-OH-C12 and 6-OAU increased the secretion of IL-8 from LPS-stimulated PMNs [1].in vivo: Injection of 6-OAU suspension in 1% rat serum into the rat jugular vein (10 mg/kg) leads to the elevation of a chemokine, CXCL1 concentration in the serum peaking at 3 h after the injection. In the rat air pouch model, 6-OAU at 1 mg/ml dissolved in 0.3% BSA attracted both PMNs and macrophages into the air pouch, peaking at 4 h after 6-OAU inoculation [1].
PBI-4050 acts as an agonist for GPR40 and as an antagonist or inverse agonist for GPR84.
GLPG1205 is potent, selective and orally active GPR84 (a G-protein-coupled receptor) antagonist with a favorable PK/PD profile. GLPG1205 has anti-inflammatory activity and is used for the treatment of pulmonary fibrosis[1][2].