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 potently increases metabolic efficiency. SHU9119 markedly increases mRNA levels of genes promoting lipogenesis and TAG storage in adipocytes, including stearoyl-CoA desaturase-1, lipoprotein lipase, acetyl-CoA carboxylase α, and fatty acid synthase. The blockade of CNS-Mcr via chronic intracerebroventricular infusion of SHU9119 (24 nmol/d for 7 days) increases food intake in ad libitum-fed rats compared with control. Weight gain of SHU9119 treated rats is significantly higher than control. SHU9119 increases food intake (+30%) and body fat (+50%) and decreases EE by a reduction in fat oxidation (?42%). SHU9119 impairs the uptake of VLDL-TG by BAT. SHU9119 reduces uncoupling protein-1 levels in BAT (?60%) and induces large intracellular lipid droplets, indicative of severely disturbed BAT activity [2][3].