Neuropeptide S GPCR Assays
Background of Neuropeptide S Receptor
Neuropeptide S receptor (NPSR), which has neuropeptide S (NPS) as its endogenous ligand, is a type of G-protein coupled receptor. NPSR and its related ligands have shown the ability to modulate the neuroendocrine, anxiety, and stress response, as well as the perception of panic.
Fig.1 Structure prediction of the Human Neuropeptide S Receptor. (Uniprot ID Q6W5P4; obtained from Alphafold)
Distribution and Function of Neuropeptide S Receptor
The regions in which NPSR can be found are concentrated in the central nervous system, but recent research suggests that NPSR is also expressed in specific cell types within the peripheral nervous system. NSPR has shown associations with some inflammatory diseases, such as asthma or arthritis, and is also involved in the process of stress and anxiety perception. NPSR can regulate the growth of specific types of tumor cells to a certain extent.
Mechanism of Neuropeptide S Receptor
NPSR is the only member of its family and binds NPS specifically.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| NPS receptor | NPSR1 |
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Assay List of Neuropeptide S Receptor
Creative Biolabs can provide a range of assays of neuropeptide S receptor. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Identification of a novel neuropeptide S receptor antagonist scaffold based on the SHA-68 core |
| Journal | Pharmaceutical |
| Published | 2021 |
| Abstract | NPSR exists widely in the entire central nervous system (CNS), and the NPS system mediated by it is involved in emotional control, anxiety coping, and memory consolidation behaviors. However, the exact connectivity of NPSR and NPS-expressing neurons is still under investigation, many basic elements of the system are still to be elucidated, and its drug and therapeutic potential need to be further explored. The development of NPSR agonists and antagonists can enhance memory, control drug addiction, or be used as a tool compound for NSPR neurological research. In previous studies, targeted NPSR antagonists have only reported limited structure-activity relationships, which often means that more possible improved analogs can be produced through structural modification. In this experiment, the researchers eliminated the chiral center by replacing the carbamate nitrogen in SHA with an alkene and adding a double bond at the bicyclic linkage, a design that preserves the overall geometry of SHA while maintaining the critical pharmacodynamic elements, which have greatly advanced the design ideas and research prospects of NSPR neurological drugs. |
| Result |
This study evaluates a series of novel NSPR antagonists by modifying and engineering the SHA framework of classical drug molecules. Data shows that when the oxazolidinone core remains intact, the diaryl structure of SHA is a manifestation of its high antagonism efficiency, which makes modification very difficult and easily produces diastereoisomers affecting subsequent drug analysis. With an in-depth understanding of the key properties of the SHA scaffold, the experimental team added a double bond at the SHA bicyclic link, leaving the remaining palm center on the aryl ring of the oxazolidinone core. This design retained the overall shape of the SHA, but differential modifications and chemical manipulations of the diaryl ring system are permitted. Based on this, experimenters designed and synthesized two small molecule compounds with different binding sites. Intensive studies on selected compound 14b revealed that substituting the aryl ring enhances the drug-like properties and solubility of such compounds and exhibits different antagonist potencies. Compound 14b exhibited a strong blocking effect of NPS stimulation in vitro, and pharmacokinetic evaluation proved that 14b reached the CNS at a therapeutic concentration with a short half-life. Results show that compound 14b has stronger in vivo activity and retains a part of the antagonistic effect of SHA, and the improved compound 14b shows the application potential of NPSR antagonists. Overall, the researchers have developed a new approach to designing NPSR antagonist molecules and obtained novel molecular scaffolds with enhanced properties that can be used as tool molecules for NPSR neural research in the future.
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Fig.2 Pharmacokinetic study of 14b in C57/Bl6 mice. (Zarkin, 2021)
Reference
- arkin, A.; et al. Identification of a novel neuropeptide S receptor antagonist scaffold based on the SHA-68 core. Pharmaceutical. 2021, 14: 1024.
