6-OAU

6-OAU is a synthetic agonist for GPR84.

GPR84, a Gαi protein-coupled receptor, is activated by medium-chain free fatty acids, but only at micromolar concentrations. GPR84 is also a putative receptor for medium-chain fatty acids. GPR84 is expressed in leukocytes and its expression can be further induced by LPS.

In vitro: A previous study identified 6-OAU as a surrogate agonist for GPR84. It was found that 6-OAU and potential ligands were able to stimulate [(35)S]GTP binding and accumulate phosphoinositides in a GPR84-dependent manner. Moreover, 6-OAU could internalize GPR84-EGFP from the cell surface. In addition, results showed that both 6-OAU and the potential ligands could elicite chemotaxis of human polymorphonuclear leukocytes (PMNs) and macrophages and amplify LPS-stimulated production of the proinflammatory cytokine IL-8 from PMNs and TNFα from macrophages [1].

In vivo: Animal study found that the iv injection of 6-OAU was able to raise the blood CXCL1 level in rats. In addition, the inoculation of 6-OAU into the rat air pouch could accumulate PMNs and macrophages in the site [1].

Clinical trial: So far, no clinical study has been conducted.

Reference:
[1] Suzuki, M. ,Takaishi, S.,Nagasaki, M., et al. Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor. The Journal of Biological Chemisty 288(15), 10684-10691 (2013).