TCS 3035 is a potent and selective GPR35 agonist.
tcs3035, a gpr35 agonist, shows significantly high potency at rat and human gpr35 orthologs with pec50 values of 5.13 and 5.86, respectively [1]. g protein-coupled receptors (gpcrs) are the largest and most studied group of transmembrane polypeptides. gpr35 is a poorly characterized g protein-coupled receptor that plays an important role in immune-modulation, gastric function and the regulation of insulin secretion. gpr35 is predominantly expressed in the gastro-intestinal tract and immune tissues. the tryptophan metabolite kynurenic acid has been suggested to be the endogenous ligand for gpr35 [1].
mutation to alanine of the conserved arginine at position 3.36 in either flag-hgpr35-eyfp or flag-rgpr35-eyfp resulted in a complete loss of agonist function of tcs3035 [1]. in addition, tcs3035-induced internalization of gpr35 is correlated with tcs3035 potency in receptor-β-arrestin-2 interaction bret assays. mutation to alanine of tyrosine 3.32 in transmembrane domain iii abolished β-arrestin-2 recruitment in response to tcs3035 [1].
1. jenkins l, alvarez-curto e, campbell k, de munnik s, canals m, schlyer s, et al. agonist activation of the g protein-coupled receptor gpr35 involves transmembrane domain iii and is transduced via galpha(1)(3) and beta-arrestin-2. br j pharmacol. 2011;162(3):733-48.
