J Med Chem. 2004 Mar 25;47(7):1602-1604.
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.
Vos TJ, Caracoti A, Che JL, Dai M, Farrer CA, Forsyth NE, Drabic SV, Horlick RA, Lamppu D, Yowe DL, Balani S, Li P, Zeng H, Joseph IB, Rodriguez LE, Maguire MP, Patane MA, Claiborne CF.
Departments of Medicinal Chemistry, Molecular & Cellular Pharmacology, and Drug Metabolism & Pharmacokinetics Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, Massachusetts 02139 and Department of Cancer Chemotherapeutics, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064.
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. |
