2. Academic Validation
  3. Discovery of a Human Neuromedin U Receptor 1-Selective Hexapeptide Agonist with Enhanced Serum Stability

Discovery of a Human Neuromedin U Receptor 1-Selective Hexapeptide Agonist with Enhanced Serum Stability

  • J Med Chem. 2017 Jun 22;60(12):5228-5234. doi: 10.1021/acs.jmedchem.7b00694.
Kentaro Takayama 1,  Kenji Mori 2,  Akiko Tanaka 3,  Erina Nomura 1,  Yuko Sohma 1,  Miwa Mori 2,  Akihiro Taguchi 1,  Atsuhiko Taniguchi 1,  Toshiyasu Sakane 4,  Akira Yamamoto 3,  Naoto Minamino 5,  Mikiya Miyazato 2,  Kenji Kangawa 2,  Yoshio Hayashi 1
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
  • 2 Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute , 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
  • 3 Department of Biopharmaceutics, Kyoto Pharmaceutical University , 5 Misasaginakauchi-cho, Yamashina, Kyoto 607-8414, Japan.
  • 4 Laboratory of Pharmaceutical Technology, Kobe Pharmaceutical University , 4-19-1 Motoyamakitamachi, Higashinada, Kobe, Hyogo 658-8558, Japan.
  • 5 Omics Research Center, National Cerebral and Cardiovascular Center , 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
PMID: 28548497 DOI: 10.1021/acs.jmedchem.7b00694
Abstract

Neuromedin U (NMU) activates two NMU receptors (NMUR1 and NMUR2) and is a useful antiobesity drug lead. We report discovery of a hexapeptide agonist, 2-thienylacetyl-Trp1-Phe(4-F)2-Arg3-Pro4-Arg5-Asn6-NH2 (4). However, the NMUR1 selectivity and serum stability of this agonist were unsatisfactory. Through a structure-activity relationship study focused on residue 2 of agonist 4, serum stability, and pharmacokinetic properties, we report here the discovery of a novel NMUR1 selective hexapeptide agonist 7b that suppresses body weight gain in mice.

Figures
Products