title: Serendipitous discovery of a new class of agonists for the melanocortin 1 and 4 receptors and a new class of cyclophanes.
abstract: A new class of melanocortin 4 receptor (MC4r) agonists was discovered from an unexpected sidereaction in which formaldehyde caused cyclization. These cyclophanes were found to be sub micromolar agonists of the MC1 and MC4 and were less potent on the MC3 and MC5 receptor. They were shown to compete with the peptidic antagonist SHU9119 for binding to the MC4 receptor. In an acute feeding study in Sprague Dawley rats, food intake was reduced more than 50% versus vehicle after 3 h at a dose of 1 mg/kg.
authors.affiliation: Department of Protein & Peptide Chemistry, Novo Nordisk, Novo Nordisk Park, Måløv, Denmark. kcf@novonordisk.com
authors.forename: Kilian
authors.initials: K
authors.lastname: Conde-Frieboes
authors.forename: Michael
authors.initials: M
authors.lastname: Ankersen
authors.forename: Jens
authors.initials: J
authors.lastname: Breinholt
authors.forename: Birgit Sehested
authors.initials: BS
authors.lastname: Hansen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Raun
authors.forename: Henning
authors.initials: H
authors.lastname: Thøgersen
authors.forename: Birgitte S
authors.initials: BS
authors.lastname: Wulff
mesh_terms: D000818:Animals; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D044102:Receptor, Melanocortin, Type 1 / Q000819:agonists*; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D000097566:Cyclophanes
chemical_list: D004988:Ethers, Cyclic; D010880:Piperidines; D044102:Receptor, Melanocortin, Type 1; D044105:Receptor, Melanocortin, Type 4; C121239:cyclophane 1; D000097566:Cyclophanes