MK-5046

MK-5046 is a novel BRS-3 agonist, binds to BRS-3 with high affinity (mouse Ki = 1.6 nM, human Ki = 25 nM).IC50 value: 1.6 nM (Ki, for mouse), 25 nM (Ki, for human) [1]Target: BRS-3in vitro: MK-5046 is a novel BRS-3 agonist, with improved BRS-3 potency, specificity, and pharmacokinetic properties that allows in-depth investigation of BRS3 agonism in preclinical species and is also potentially suitable for use in humans. MK-5046 exhibits no appreciable binding activity at the neuromedin B and gastrin-releasing peptide receptors, as well as many other receptors, ion channels, and enzymes. In a cell-based Ca2+ mobilization functional assay, MK-5046 activates human BRS-3 with similar agonist efficacy as the peptide BRS-3 agonist.[1] MK-5046 is a potent, selective bombesin receptor subtype-3 agonist for the treatment of obesity.[2]in vivo: MK-5046 is the first BRS-3 agonist with properties suitable for use in larger mammals. In dogs, MK-5046 treatment produced statistically significant and persistent weight loss, which was initially accompanied by increases in body temperature and heart rate that abated with continued dosing. MK-5046 also effectively reduced body weight in rats and caused modest increases in body temperature, heart rate, and blood pressure. MK-5046 in rodents and dogs and further support BRS-3 agonism as a new approach to the treatment of obesity.[1]

[1]. Guan XM, et al. Antiobesity effect of MK-5046, a novel bombesin receptor subtype-3 agonist. J Pharmacol Exp Ther. 2011 Feb;336(2):356-364. [2]. Sebhat IK, et al. Discovery of MK-5046, a Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity. ACS Med Chem Lett. 2010 Oct 18;2(1):43-47.