Resomelagon

Resomelagon (AP1189) is a potent, orally active melanocortin receptor (MR) agonist. Resomelagon induces ERK1/2 phosphorylation and Ca2+ mobilization. Resomelagon has anti-inflammatory activity. Resomelagon can be used for obesity and chronic inflammation research[1][2].

Research Areas >> Metabolic Disease

Signaling Pathways >> GPCR/G Protein >> Melanocortin Receptor

Resomelagon (AP1189) (0-1000 μM; 8 min; HEK293A cells) promotes melanocortin signal transduction through ERK1/2 phosphorylation and Ca2+ mobilization[1]. Resomelagon (AP1189) (1 nM; 30 min; peritoneal macrophages) has anti-inflammatory activity and inhibits TNF-α release and efferocytosis[1]. Western Blot Analysis[1] Cell Line: HEK293A cells Concentration: 0-1000 μM Incubation Time: 8 minutes Result: Increased the expression of ERK1/2 phosphorylation in a dose-dependent manner.

Resomelagon (AP1189) (0-10 mg/kg; i.p., i.v. and p.o.; for 24 h; male C57BL/6J wild-type (WT) and BALB/c mice) promotes resolution of acute inflammation in vivo[1]. Resomelagon (AP1189) (25-50 mg/kg; p.o.; daily, for 8 d; male C57BL/6J wild-type (WT) and BALB/c mice) reduces arthritis in mice[1]. Animal Model: Male C57BL/6J wild-type (WT) and BALB/c mice[1] Dosage: 0, 0.1, 1 and 10 mg/kg Administration: Oral administration, intraperitoneal injection and intravenous injection; for 24 hours Result: Inhibited neutrophil and monocyte infiltration in a dose-dependent manner. Animal Model: Male C57BL/6J wild-type (WT) and BALB/c mice[1] Dosage: 25 and 50 mg/kg Administration: Oral administration; daily; for 8 days Result: Reduced all signs of arthritis measured, including clinical score (−42%), paw swelling (−87%), proportion of animals with all four paws affected (−50%), and the severity of the inflammation (−70%).

[1]. Montero-Melendez T, et, al. Biased agonism as a novel strategy to harness the proresolving properties of melanocortin receptors without eliciting melanogenic effects. J Immunol. 2015 Apr 1;194(7):3381-8.

[2]. WHO Drug Information. International Nonproprietary Names for Pharmaceutical