AP1189 (acetate)

AP1189 is a biased agonist of melanocortin receptor 1 (MC1R) and MC3R.¹ It induces ERK1 and ERK2 phosphorylation but not canonical cAMP production in HEK293 cells expressing human MC1R or MC3R when used at concentrations ranging from 10 pM to 1 mM. AP1189 (0.1-10 nM) reduces zymosan-induced IL-1β, IL-6, and TNF-α production in primary peritoneal macrophages isolated from wild-type but not Mc3r^-/- mice. It reduces zymosan-induced TNF-α production but has no effect on IL-1β or IL-6 production in primary macrophages isolated from Mc1r^-/- mice. AP1189 promotes efferocytosis in primary mouse macrophages. In vivo, AP1189 (1, 3, and 10 mg/kg) reduces peritoneal neutrophil infiltration in a mouse model of zymosan-induced acute peritonitis. AP1189 (50 mg/kg) reduces paw volume, the number of paws affected, and disease severity in a mouse model of arthritogenic serum-induced arthritis.

WARNING This product is not for human or veterinary use.

1. Montero-Melendez, T., Gobbetti, T., Cooray, S.N., et al. Biased agonism as a novel strategy to harness the proresolving properties of melanocortin receptors without eliciting melanogenic effects. J. Immunol. 194(7), 3381-3388 (2015).