title: Identification of 2-[2-[2-(5-bromo-2- methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model.
abstract: The melanocortin 4 receptor (MC4R) plays an important role in body weight regulation and energy homeostasis. Administration of peptidic MC4R antagonists (usually by intracerebro ventricular injection) has been shown in the literature to increase body weight and/or food intake in several rodent models. We report here the identification of a novel nonpeptidic MC4R antagonist and its effects on tumor-induced weight loss in mice following peripheral administration.
authors.affiliation: Department of Medicinal Chemistry, Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, Massachusetts 02139, USA. tricia.vos@mpi.com
authors.forename: Tricia J
authors.initials: TJ
authors.lastname: Vos
authors.forename: Andrei
authors.initials: A
authors.lastname: Caracoti
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Che
authors.forename: Mingshi
authors.initials: M
authors.lastname: Dai
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Farrer
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Forsyth
authors.forename: Stacey V
authors.initials: SV
authors.lastname: Drabic
authors.forename: Robert A
authors.initials: RA
authors.lastname: Horlick
authors.forename: Diana
authors.initials: D
authors.lastname: Lamppu
authors.forename: David L
authors.initials: DL
authors.lastname: Yowe
authors.forename: Suresh
authors.initials: S
authors.lastname: Balani
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Hang
authors.initials: H
authors.lastname: Zeng
authors.forename: Ingrid B J K
authors.initials: IB
authors.lastname: Joseph
authors.forename: Luis E
authors.initials: LE
authors.lastname: Rodriguez
authors.forename: Martin P
authors.initials: MP
authors.lastname: Maguire
authors.forename: Michael A
authors.initials: MA
authors.lastname: Patane
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Claiborne
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001550:Benzamidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004614:Emaciation / Q000188:drug therapy* / Q000209:etiology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000150:complications*; D011869:Radioligand Assay; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: C484860:2-(2-(2-(5-bromo-2-methoxyphenyl)ethyl)-3-fluorophenyl)-4,5-dihydro-1H-imidazole; D001550:Benzamidines; D007093:Imidazoles; D044105:Receptor, Melanocortin, Type 4