G- protein coupled receptor 35 (GPR35) is an "orphan" GPCR, whose native ligand is still unknown. It was shown to be involved in the modulation of synaptic transmission, nociception, neuropathic and inflammatory pain, and in various diseases including ulcerative colitis and primary sclerosing cholangitis¹ and hence there is a great therapeutic potential in studying its activity.

In vitro, GPR35 is stimulated by high concentrations of a number of small molecules, including kynurenic acid, 2-oleoyllysophosphatidic acid, DHICA, reverse T3, cGMP and it has a wide range of synthetic agonists and antagonists that either activate or inactivate it, respectively (Summarized in²).

 GPR35 is composed of seven trans-membrane domains, and it was shown to share structural homology with various receptors for chemokines; chemotactic cytokines that direct the traffic of leukocytes and other cells in the body. It was shown to be activated by chemokine CXCL17, and hence the role of a chemokine receptor was also assigned to it³.

GPR35 expression has been identified within discrete regions of the central nervous system (CNS) and peripheral nervous system, and lower levels in heart, lung and skeletal muscle, and also in the lower gut and colon and by various white cell groups, including numerous dendritic cell and monocyte populations⁴.