論文

査読有り 国際誌
2017年7月27日

Potent Body Weight-Lowering Effect of a Neuromedin U Receptor 2-selective PEGylated Peptide.

Journal of medicinal chemistry
  • Yoko Kanematsu-Yamaki
  • Naoki Nishizawa
  • Tomoko Kaisho
  • Hiroaki Nagai
  • Taisuke Mochida
  • Tomoko Asakawa
  • Hiroshi Inooka
  • Katsuko Dote
  • Hisashi Fujita
  • Kouta Matsumiya
  • Hideki Hirabayashi
  • Junichi Sakamoto
  • Tetsuya Ohtaki
  • Shiro Takekawa
  • Taiji Asami
  • 全て表示

60
14
開始ページ
6089
終了ページ
6097
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1021/acs.jmedchem.7b00330

Neuromedin U (NMU) is a neuropeptide that mediates a variety of physiological functions via its receptors, NMUR1 and NMUR2. Recently, there has been an increased focus on NMU as a promising treatment option for diabetes and obesity. A short form of NMU (NMU-8) has potent agonist activity for both receptors but is metabolically unstable. Therefore, we designed and synthesized NMU-8 analogues modified by polyethylene glycol (PEG; molecular weight, 20 kDa; PEG20k) via a linker. 3-(2-Naphthyl)alanine substitution at position 19 increased NMUR2 selectivity of NMU-8 analogues with retention of high agonist activity. Compound 37, an NMUR2-selective PEG20k analogue containing piperazin-1-ylacetyl linker, exhibited a potent body weight-lowering effect with concomitant inhibition of food intake in a dose-dependent manner (body weight loss of 12.4% at 30 nmol/kg) by once-daily repeated dosing for 2 weeks in mice with diet-induced obesity.

リンク情報
DOI
https://doi.org/10.1021/acs.jmedchem.7b00330
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28657315
ID情報
  • DOI : 10.1021/acs.jmedchem.7b00330
  • PubMed ID : 28657315

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