Growth hormone secretagogue receptor antagonists as anti-obesity therapies? Still an open question.
Ghrelin woas recently de-orphaned as an endogenous ligand of growth hormone secretagogue receptor (GHS-R), and is implicated as a short-term meal initiator and a long-term energy balance regulator. Administration of ghrelin causes increases in food intake and body weight in both rodents and humans. Inhibiting its actions with GHS-R anti-sense oligonucleotides, anti-ghrelin antibodies, and peptide antagonists leads to decreased food intake and weight loss in rodents. Despite the much-publicized promise of providing a novel approach for anti-obesity treatment, limited progress has been made in developing small-molecule GHS-R antagonists and no such compound has been advanced to clinical trials. This review will summarize the recent progress in small-molecule GHS-R antagonists and offer some insight into this area of research based on the experience at Abbott Laboratories.
Zhao
Hongyu
H
Abbott Laboratories, Metabolic Disease Research, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA. Hongyu.zhao@abbott.com
Liu
Gang
G
D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054440:Receptors, Ghrelin
D019440:Anti-Obesity Agents; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin