title: Discovery of Novel Potent and Selective Agonists at the Melanocortin-3 Receptor.
abstract: The melanocortin receptors 3 and 4 control energy homeostasis, food-intake behavior, and correlated pathophysiological conditions. The melanocortin-4 receptor (MC4R) has been broadly investigated. In contrast, the knowledge related to physiological roles of the melanocortin-3 receptor (MC3R) is lacking because of the limited number of known MC3R selective ligands. Here, we report the design, synthesis, biological activity, conformational analysis, and docking with receptors of two potent and selective agonists at the human MC3 receptor.
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II , Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II , Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Merlino
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona , Tucson, Arizona 85721, United States.
authors.forename: Minying
authors.initials: M
authors.lastname: Cai
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II , Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Brancaccio
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II , Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Ali Munaim
authors.initials: AM
authors.lastname: Yousif
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II , Via D. Montesano, 49, 80131, Naples, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona , Tucson, Arizona 85721, United States.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II , Via D. Montesano, 49, 80131, Naples, Italy.|CIRPEB: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples Federico II , 80134, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
mesh_terms: D000242:Cyclic AMP / Q000096:biosynthesis; D057809:HEK293 Cells; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D044104:Receptor, Melanocortin, Type 3 / Q000819:agonists*; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000378:metabolism; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C505392:MC3R protein, human; C470072:MC4R protein, human; D009842:Oligopeptides; D044102:Receptor, Melanocortin, Type 1; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D044101:Receptors, Melanocortin; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; C086971:melanocortin 5 receptor; C103272:SHU 9119; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP