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 journalArticle

2 Citations (Scopus)

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Synthesis and in Vitro Evaluation of Stabilized and Selective Neuromedin U-1 Receptor Agonists'. Together they form a unique fingerprint.

  • Cite this

    De Prins, A., Martin, C., Van Wanseele, Y., Tömböly, C., Tourwé, D., Caveliers, V., Holst, B., Van Eeckhaut, A., Rosenkilde, M. M., Smolders, I., & Ballet, S. (2018). Synthesis and in Vitro Evaluation of Stabilized and Selective Neuromedin U-1 Receptor Agonists. ACS Medicinal Chemistry Letters, 9(5), 496-501. https://doi.org/10.1021/acsmedchemlett.8b00105