Nagaaki Sato1, Yoshio Ogino, Satoshi Mashiko, Makoto Ando. 1. 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
Abstract
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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Lydiane Funkelstein; W Douglas Lu; Britta Koch; Charles Mosier; Thomas Toneff; Laurent Taupenot; Daniel T O'Connor; Thomas Reinheckel; Christoph Peters; Vivian Hook Journal: J Biol Chem Date: 2012-03-05 Impact factor: 5.157
Authors: Gopi Kumar Mittapalli; Danielle Vellucci; Jun Yang; Marion Toussaint; Shaun P Brothers; Claes Wahlestedt; Edward Roberts Journal: Bioorg Med Chem Lett Date: 2012-04-30 Impact factor: 2.823
Authors: Shuanghua Hu; Yazhong Huang; Milind Deshpande; Guanglin Luo; Marc A Bruce; Ling Chen; Gail Mattson; Lawrence G Iben; Jie Zhang; John W Russell; Wendy J Clarke; John B Hogan; Astrid Ortiz; Oliver Flint; Andrew Henwood; Qi Gao; Ildiko Antal-Zimanyi; Graham S Poindexter Journal: ACS Med Chem Lett Date: 2012-01-04 Impact factor: 4.345