Synthesis and in Vitro Evaluation of Stabilized and Selective Neuromedin U-1 Receptor Agonists

An De Prins, Charlotte Martin, Yannick Van Wanseele, Csaba Tömböly, Dirk Tourwé, Vicky Caveliers, Birgitte Holst, Ann Van Eeckhaut, Mette M. Rosenkilde, Ilse Smolders, Steven Ballet

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
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Abstract

Neuromedin U (NMU) is a multifunctional neuropeptide which is characterized by a high conservation through all species. Herein, we describe the synthesis of a novel set of NMU-analogs based on the truncated NMU-8. Through combination of previously reported modifications, an elaborate structure-activity relationship study was performed aiming for the development of peptides with an increased selectivity toward NMU receptor 1 (NMUR1). Compound 7 possessed the highest NMUR1 selectivity (IC 50 = 0.54 nM, selectivity ratio = 5313) together with an increased potency (EC 50 = 3.7 nM), an 18% increase of the maximal effect at NMUR1, and a higher resistance against enzymatic degradation as compared to the native NMU-8. The development of a potent NMUR1 agonist with extended half-life could represent an attractive tool to further unveil the role of NMUR1 in NMU signaling.

Original languageEnglish
Pages (from-to)496–501
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume9
Issue number5
DOIs
Publication statusPublished - 10 May 2018

Bibliographical note

doi: 10.1021/acsmedchemlett.8b00105

Keywords

  • NMU-8
  • NMUR1
  • Neuromedin U (NMU)
  • Neuromedin U receptor agonist
  • in vitro plasma stability

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