SHU 9119 is an effective human melanocortin 3 and 4 receptors (MC3/4R) antagonist and a partial MC5R agonist (IC50: 0.23, 0.06, and 0.09 nM for human MC3R, MC4R and MC5R, respectively).

MC3R:0.23 nM, MC5R:0.23 nM, MC4R:0.23 nM

SHU9119 treatment significantly enhances metabolic efficiency by increasing mRNA levels of genes involved in lipogenesis and TAG storage in adipocytes, including stearoyl-CoA desaturase-1, lipoprotein lipase, acetyl-CoA carboxylase α, and fatty acid synthase. Chronic intracerebroventricular infusion of SHU9119 (24 nmol/d for 7 days) in ad libitum-fed rats increases food intake and weight gain compared to control. SHU9119 results in a 30% increase in food intake, a 50% increase in body fat, and a 42% reduction in energy expenditure due to decreased fat oxidation. It hampers VLDL-TG uptake and reduces uncoupling protein-1 levels in BAT by 60%, causing large intracellular lipid droplets and severely disturbed BAT activity [2][3].