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

作者：Takayama Kentaro; Mori Kenji; Tanaka Akiko; Nomura Erina; Sohma Yuko; Mori Miwa; Taguchi Akihiro; Taniguchi Atsuhiko; Sakane Toshiyasu; Yamamoto Akira; Minamino Naoto; Miyazato Mikiya; Kangawa Kenji; Hayashi Yoshio

来源：Journal of Medicinal Chemistry, 2017, 60(12): 5228-5234.

DOI：10.1021/acs.jmedchem.7b00694

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)-Arg(3)Pro(4)-Arg(5)-Asn(6)-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.

• 出版日期2017-6-22