Modulation of neuropeptide Y receptors for the treatment of obesity.
BACKGROUND
Neuropeptide Y (NPY) has been demonstrated to have critical roles in the physiological control of appetite and energy homeostasis through NPY Y1, Y2, Y4 and Y5 receptors. A number of synthetic ligands for NPY receptor subtypes have been developed to date, with Y5 receptor antagonists and Y2 and Y4 receptor agonists advancing into clinical trials.


METHODS
A survey of the scientific and patent literature since mid-2006 is presented.


CONCLUSIONS
In addition to the specific modulation of respective NPY receptor subtypes, recent investigations have revealed that modulation of multiple NPY receptor subtypes produces additive or even synergistic anti-obesity effects. Development of reliable small molecule Y1, Y2 and Y4 receptor ligands would greatly accelerate investigations and drug discovery.
Sato
Nagaaki
N
Department of Medicinal Chemistry, Taisho Pharmaceutical Co. Ltd., Taisho Research Laboratories, 1-403 Yoshinocho, Kitaku, Saitama, Japan. nagaaki.sato.cho@po.rd.taisho.co.jp
Ogino
Yoshio
Y
Mashiko
Satoshi
S
Ando
Makoto
M
D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D016896:Treatment Outcome
D019440:Anti-Obesity Agents; D008024:Ligands; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y