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

Research output: Contribution to journalJournal articleResearchpeer-review

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

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 (IC50 = 0.54 nM, selectivity ratio = 5313) together with an increased potency (EC50 = 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
JournalACS Medicinal Chemistry Letters
Issue number5
Pages (from-to)496-501
Number of pages6
Publication statusPublished - 10 May 2018

ID: 209112675