UR-PI376 is a histamine H4 receptor agonist ( hH4R agonist) (pEC50 = 7.47, alpha = 0.93) showing negligible hH1R and hH2R activities and significant selectivity over the hH3R (pKB = 6.00, alpha = -0.28), as determined in steady-state GTPase assays using membrane preparations of hH(x)R-expressing Sf9 cells. Modeling of the binding mode of UR-PI376 suggests that the cyanoguanidine moiety forms charge-assisted hydrogen bonds not only with the conserved Asp-94 but also with the hH4R-specific Arg-341 residue.
