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ID: ALA4145600
Journal: ACS Med Chem Lett
Title: Synthesis and in Vitro Evaluation of Stabilized and Selective Neuromedin U-1 Receptor Agonists.
Authors: De Prins A, Martin C, Van Wanseele Y, Tömböly C, Tourwé D, Caveliers V, Holst B, Van Eeckhaut A, Rosenkilde MM, Smolders I, Ballet S.
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.
CiteXplore: 29795766