HS-024 is a cyclic peptide antagonist of melanocortin receptor 4 (MC4R; Ki = 0.29 nM).1 It is selective for MC4R over MC1R, MC3R, and MC5R (Kis = 18.6, 5.45, and 3.29 nM, respectively). HS-024 (100 nM) inhibits cAMP accumulation induced by α-melanocyte-stimulating hormone (α-MSH) in COS-1 cells expressing human MC1R, MC3R, MC4R, or MC5R. It increases food intake in rats when administered at doses of 0.3, 1, or 3 nmol/animal. Intrathecal administration of HS-024 (1.5 nmol/animal) inhibits mechanical allodynia at 30 minutes post-injection in a rat model of spinal nerve ligation-induced neuropathic pain.2 It reduces stress-induced reinstatement of nicotine seeking in the foot shock test in rats.3
References:
[1]. Kask, A., Mutulis, F., Muceniece, R., et al.Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): Evaluation in vitro and in vivoEndocrinology139(12)5006-5014(1998).
[2]. Bertorelli, R., Fredduzzi, S., Tarozzo, G., et al.Endogenous and exogenous melanocortin antagonists induce anti-allodynic effects in a model of rat neuropathic painBehav. Brain Res.157(1)55-62(2005).
[3]. Qi, X., Yamada, H., Corrie, L.W., et al.A critical role for the melanocortin 4 receptor in stress-induced relapse to nicotine seeking in ratsAddict. Biol.20(2)324-335(2015).