title: Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.
abstract: The discovery of the endogenous melanocortin agonists in the 1950s have resulted in sixty years of melanocortin ligand research. Early efforts involved truncations or select modifications of the naturally occurring agonists leading to the development of many potent and selective ligands. With the identification and cloning of the five known melanocortin receptors, many ligands were improved upon through bench-top in vitro assays. Optimization of select properties resulted in ligands adopted as clinical candidates. A summary of every melanocortin ligand is outside the scope of this review. Instead, this review will focus on the following topics: classic melanocortin ligands, selective ligands, small molecule (non-peptide) ligands, ligands with sex-specific effects, bivalent and multivalent ligands, and ligands advanced to clinical trials. Each topic area will be summarized with current references to update the melanocortin field on recent progress. This article is part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong Tao.
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Ericson
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Lensing
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Katlyn A
authors.initials: KA
authors.lastname: Fleming
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Schlasner
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Skye R
authors.initials: SR
authors.lastname: Doering
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: chaskell@umn.edu.
authors.forename: Carrie
authors.initials: C
authors.lastname: Haskell-Luevano
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D053486:Melanocortins / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D044101:Receptors, Melanocortin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D008024:Ligands; D053486:Melanocortins; D044101:Receptors, Melanocortin; D054852:Small Molecule Libraries
keywords: Bivalent/multivalent ligands; Clinical trials; Selective ligands; Sexual dimorphism; Small molecules