GD134

GD134 (72.HCl) is a dual H1R/H4R ligand with pK_i values of 7.54 and 7.67 for the human receptors, respectively, and maintains nanomolar affinity at mouse, rat, and monkey H4R orthologs^[1].
GD134 antagonizes human and mouse H1R/H4R in the CRE-luciferase assay, with pK_b values of 6.64 and 7.31 for human H1R/H4R and 6.53 and 7.83 for mouse H1R/H4R, and exhibits inverse agonist activity at human H4R^[1].
GD134 is metabolically stable in human and rat liver microsomes, but is rapidly cleared in mouse liver microsomes^[1].
GD134 exhibits high plasma protein binding (approximately 98%), with a free unbound fraction of approximately 1%^[1].
GD134 exhibits moderate Caco-2 permeability (P_app 25.6 × 10^-6 cm/s)^[1].
GD134 (10 μM) is non-mutagenic in the Ames test, including in the presence of rat liver S9 metabolites^[1].
GD134 (10 μM) shows negligible hERG binding (pK_i <5), but exhibits measurable off-target activity at several aminergic receptors and inhibits hERG in functional patch-clamp experiments^[1].
GD134 (up to 1000 μM) does not show cytotoxicity^[1].