Open AccessEvaluation of AMG 076, a potent and selective MCHR 1 antagonist, in rodent and primate obesity models
Author(s) -
Motani Alykhan S.,
Luo Jian,
Liang Lingming,
Mihalic Jeffrey T.,
Chen Xiaoqi,
Tang Liang,
Li Leping,
Jaen Juan,
Chen JinLong,
Dai Kang
Publication year - 2013
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.3
Subject(s) - antagonist , obesity , knockout mouse , hormone , pharmacology , endocrinology , food intake , body weight , rodent , medicine , weight loss , receptor , biology , ecology
Melanin‐concentrating hormone ( MCH ) regulates food intake through activation of the receptor, MCHR 1. We have identified AMG 076 as an orally bioavailable potent and selective small molecule antagonist of MCHR 1. In mouse models of obesity, AMG 076 caused a reduction in body weight gain in wild‐type ( MCHR 1+/+) but not in knockout ( MCHR 1−/−) mice. The body weight reduction was associated with decreases in food intake and increases in energy expenditure. Importantly, we show that these MCHR 1‐dependent effects of AMG 076 were also reflected in improved metabolic phenotypes, increased glucose tolerance and insulin sensitivity. Preliminary data on effects of AMG 076 in obese cynomolgus monkeys are also presented.