Neuromedin U GPCR Assays
Background of Neuromedin U Receptors
Neuromedin U receptors (NMURs), which comprise 2 subtypes: neuromedin U receptor 1 (NMU1 receptor) and neuromedin U receptor 2 (NMU2 receptor), are members of G-protein coupled receptors. NMURs can bind neuromedin U and neuromedin S, thus playing roles in feeding behavior, muscle contraction, and other activities of human bodies.
Fig.1. Structure of the Neuromedin U receptor 1 of a Zebrafish. (Uniprot ID F1R3B8; obtained from Alphafold)
Distribution and Function of Neuromedin U Receptors
Neuromedin U Receptors are distributed throughout the human body. NMU1 receptor is mainly expressed in the periphery, with a small distribution in the central nervous system, and the NMU2 receptor is the opposite. The widespread distribution of NMUs in the human body suggests that they have many functions such as the regulation of smooth muscle contraction, energy homeostasis, secretion of gastric acid, and control of feeding rhythm.
Subtypes and Mechanisms of Neuromedin U Receptors
NMU1 receptor and NMU2 receptor have been cloned since 2000. Despite the differences in distribution, they still have similar mechanisms and structures.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
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M1 receptor |
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NMU2 receptor |
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Assay List of Neuromedin U Receptors
Creative Biolabs can provide a range of assays of neuromedin U receptors. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title |
Small-molecule Neuromedin U Receptor 2 agonists suppress food intake and decrease visceral fat in animal models |
| Journal |
Pharmacology Research & Perspectives |
| Published |
2018 |
| Abstract |
Obesity is a common and disturbing health problem for which there are currently no effective medical or surgical interventions. In previous studies, it was confirmed that the deficiency of Neuromedin U (NMU) would lead to hyperphagia, decreased metabolism, and obesity in mice, and the inhibition of NMU reversed this phenomenon, suggesting that NMU and its related receptors play a role in regulating body weight and diet rhythmic, especially NMUR2, which is located in the central nervous system. NMUR2 is enriched in the hypothalamus, and the knockout experiment of NMUR2 confirmed its regulatory role in feeding, body weight, and blood activity, making the activation of NMUR2 show the prospect of treating obesity. The main goal of this research is to screen, verify, and identify feasible drug molecules and targets by means of pharmacology and molecular biology. In this study, the researchers verified the role of NMUR2 in obesity control, explored possible signal response pathways, and screened two small molecules of NMUR2 agonist drugs with potential for obesity control. |
| Result |
In the experiment, two small molecule agonists of NMUR2, NY0116, and NY0128, were discovered through high-throughput screening, and the synthesized compounds were tested by mass spectrometry and purity for pharmacokinetic tests in living cells and mouse models. The data showed that both compounds showed good plasma concentrations and half-lives, and could cross the blood-brain barrier to reach the central nervous system at therapeutic concentrations. Long-term subcutaneous treatment showed that both compounds reduced body weight and lowered cholesterol levels, suggesting that NMUR2 may serve as a potential therapeutic target for obesity and metabolic disorders, and NMUR2 agonists can be used as potential tool compounds. Molecular assays showed that NMUR2 agonists reduced cAMP levels and stimulated calcium signaling in HEK293 cells. The results of the binding experiment showed that the two NMUR2 small molecule agonists did not show selectivity for NMUR2, so further structural optimization is still needed, but similar small molecules have shown therapeutic potential in obesity control and metabolic regulation. Fig.2. Chronic administration of an NMUR2 agonist reduces body weight and metabolic disturbances in mice. (Sampson, 2018) |
Reference
- Sampson, C.; et al. Small-molecule Neuromedin U Receptor 2 agonists suppress food intake and decrease visceral fat in animal models. Pharmacology Research & Perspectives. 2018, 1002: e00425.
