(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide

BeschreibungSHU9119 is an agonist of melanocortin receptor 1 (MC1R) and antagonist of MC4R (IC50s = 1.2 and 2.9 nM, respectively, for displacement of melanocortin). It induces cAMP formation in HEK293 cells expressing human MC1R (EC50 = 1.11 nM), but inhibits cAMP formation in cells expressing human MC4R. In rats, SHU9119 (24 nmol, i.c.v. per day for seven days) increases food intake, body weight, fat mass, and lean mass, with concomitant increases in blood glucose, insulin, and leptin levels via disrupted melanocortin signaling. Similarly, mice treated with SHU9119 (5 nmol/day, i.c.v.) exhibit food intake-independent increases in body weight and fat mass consequent to MC4R inhibition and subsequent brown adipose tissue dysfunction.