BMS-470539 dihydrochloride is a highly potent and selective agonist of the melanocortin-1 receptor (MC-1R; IC50: 120 nM; EC50: 28 nM) with anti-inflammatory properties. It does not activate MC-3R and is a very weak partial agonist at MC-4R and MC-5R.

An established HBL melanoma cell line stably expresses an NF-κB luciferase reporter, allowing for the observation that TNF-α at 0.5 ng/mL incites a dose-dependent escalations in NF-κB luciferase activity. Administering BMS-470539 to these HBL-NF-κB cells leads to a dose-dependent diminution in TNF-α-induced NF-κB luciferase activity, while it remains ineffective in altering luciferase reporter activity in the absence of TNF-α induction. In nontransfected HBL cells, BMS-470539 administration shows a dose-dependent deterrence of NF-κB nuclear translocation.

The treatment of BMS-470539 (2.05-18.47 mg/kg; i.v.; for 125 minutes; WT and MC1 receptor recessive e/e mice) inhibits cell emigration and adhesion with no effect on cell rolling. It also inhibits the tissue expression of CXCL1/CCL2 [3].