Discovery of a β-MSH-Derived MC-4R Selective Agonist
Journal of Medicinal Chemistry2005Vol. 48(9), pp. 3095–3098
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John P. Mayer, Hansen M. Hsiung, David B. Flora, Patrick J. B. Edwards, Dennis P. Smith, Xingyue Zhang, Robert A. Gadski, Mark L. Heiman, JeAnne Hertel, Paul J. Emmerson, Saba Husain, Thomas P. O’Brien, Steven D. Kahl, David L. Smiley, Lianshan Zhang, Richard D. DiMarchi, Liang Yan
Abstract
A series of novel, disulfide-constrained human beta-melanocyte stimulating hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food intake and body weight models.
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