Small-Molecule Neuromedin U Receptor 2 Agonists Suppress Food Intake and Decrease Visceral Fat in Animal Models

Pharmacology Research & Perspectives
Catherine M SampsonJ D Hommel

Abstract

Obesity is a growing public health concern, with 37.5% of the adult population in need of therapeutics that are more efficacious with a better side effect profile. An innovative target in this regard is neuromedin U, a neuropeptide shown to suppress food intake and attenuate weight gain in animal models. These effects of neuromedin U on feeding behavior are thought to be related to agonism at the centrally expressed neuromedin U receptor 2 (NMUR2). As peptides present unique challenges that limit their therapeutic potential, the discovery of small-molecule NMUR2 agonists is needed to validate the targets therapeutic value, but to date, none have been evaluated in any animal model of disease. We therefore assessed two small-molecule NMUR2 agonists for their in vitro signaling and their in vivo efficacy. The NMUR2 agonists were synthesized and both NMUR2 agonists, NY0116 and NY0128, decreased cAMP while stimulating calcium signaling in stably expressing NMUR2 HEK293 cells. When small-molecule NMUR2 agonists were tested in vivo, acute administration significantly decreased high-fat diet consumption. Repeated administration of the compounds decreased body weight and more specifically, decreased the percentage of visceral adipose ti...Continue Reading

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Citations

Jul 17, 2020·International Journal of Molecular Sciences·Ellen OttoJohannes Keller
Sep 19, 2019·Current Medicinal Chemistry·An De PrinsSteven Ballet

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Methods Mentioned

BETA
NMR
fluorescence imaging
pharmacotherapy

Software Mentioned

FLIPR TETRA ScreenWorks
ChemBioDraw
GraphPad
GraphPad Prism
Inveon Research Workplace

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