ML-00253764 (hydrochloride)

ML-00253764 is a melanocortin receptor 4 (MC4R) antagonist (K_i = 0.16 µM).¹ It is selective for MC4R over MC3R and MC5R (IC₅₀s = 0.32, 0.81, and 2.12 µM, respectively).² ML-00253764 (100 µM) decreases cAMP production induced by [NLE⁴,D-Phe⁷]-α-melanocyte stimulating hormone ([NDP]-α-MSH; Item No. 24475) by 20% in MC4R-expressing HEK293 cell membranes, but has no effect on cAMP levels in MC3R- or MC5R-expressing membranes. It prevents the loss of lean body mass and enhances light-phase food consumption in a Lewis lung carcinoma (LLC) mouse model but does not reduce tumor size when administered at a dose of 15 mg/kg.

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1. Vos, T.J., Caracoti, A., Che, J.L., et al. Identification of 2-{2-[2-(5-bromo-2methoxyphenyl)-ethyl]-3-fluorophenyl}-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model. J. Med. Chem. 47(7), 1602-1604 (2004).

2. Nicholson, J.R., Kohler, G., Schaerer, F., et al. Peripheral administration of a melanocortin 4-receptor inverse agonist prevents loss of lean body mass in tumor-bearing mice. J. Pharmacol. Exp. Ther. 317(2), (2006).