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.
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.
Vos
Tricia J
TJ
Department of Medicinal Chemistry, Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, Massachusetts 02139, USA. tricia.vos@mpi.com
Caracoti
Andrei
A
Che
Jennifer L
JL
Dai
Mingshi
M
Farrer
Cheryl A
CA
Forsyth
Nancy E
NE
Drabic
Stacey V
SV
Horlick
Robert A
RA
Lamppu
Diana
D
Yowe
David L
DL
Balani
Suresh
S
Li
Ping
P
Zeng
Hang
H
Joseph
Ingrid B J K
IB
Rodriguez
Luis E
LE
Maguire
Martin P
MP
Patane
Michael A
MA
Claiborne
Christopher F
CF
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
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