更新于：2024-11-01

NMUR2

更新于：2024-11-01

基本信息

别名

G-protein coupled receptor FM-4、G-protein coupled receptor TGR-1、neuromedin U receptor 2

+ [5]

简介

Receptor for the neuromedin-U and neuromedin-S neuropeptides.

关联

项与 NMUR2 相关的药物

CPN-219

靶点

NMUR2

作用机制

NMUR2 激动剂

在研机构

Tokyo University of Pharmacy & Life Science

原研机构

Tokyo University of Pharmacy & Life Science

在研适应症

肥胖

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

NMU-0002

靶点

NMUR1 x NMUR2

作用机制

NMUR1 agonists [+1]

在研机构

Takeda Pharmaceuticals LLC

原研机构

Takeda Pharmaceuticals LLC

在研适应症

肥胖

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

CPN-116

靶点

NMUR2

作用机制

NMUR2 激动剂

在研机构

Tokyo University of Pharmacy & Life Science

原研机构

Tokyo University of Pharmacy & Life Science

在研适应症

肥胖

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 NMUR2 相关的临床结果

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100 项与 NMUR2 相关的转化医学

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0 项与 NMUR2 相关的专利（医药）

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168

项与 NMUR2 相关的文献（医药）

2024-08-01·The Journal of Pain

Spinal Nmur2-positive Neurons Play a Crucial Role in Mechanical Itch

Article

作者: Xu, Jun-Feng ; Liu, Lian ; Zhu, Yan-Jing ; Liu, Yuan ; Fang, Fang ; Dou, Yan-Nong ; Lu, Ke-Xing ; Zhang, Jun

The dorsal spinal cord is crucial for the transmission and modulation of multiple somatosensory modalities, such as itch, pain, and touch. Despite being essential for the well-being and survival of an individual, itch and pain, in their chronic forms, have increasingly been recognized as clinical problems. Although considerable progress has been made in our understanding of the neurochemical processing of nociceptive and chemical itch sensations, the neural substrate that is crucial for mechanical itch processing is still unclear. Here, using genetic and functional manipulation, we identified a population of spinal neurons expressing neuromedin U receptor 2 (Nmur2⁺) as critical elements for mechanical itch. We found that spinal Nmur2⁺ neurons are predominantly excitatory neurons, and are enriched in the superficial laminae of the dorsal horn. Pharmacogenetic activation of cervical spinal Nmur2⁺ neurons evoked scratching behavior. Conversely, the ablation of these neurons using a caspase-3-based method decreased von Frey filament-induced scratching behavior without affecting responses to other somatosensory modalities. Similarly, suppressing the excitability of cervical spinal Nmur2⁺ neurons via the overexpression of functional Kir2.1 potassium channels reduced scratching in response to innocuous mechanical stimuli, but not to pruritogen application. At the lumbar level, pharmacogenetic activation of these neurons evoked licking and lifting behaviors. However, ablating these neurons did not affect the behavior associated with acute pain. Thus, these results revealed the crucial role of spinal Nmur2⁺ neurons in mechanical itch. Our study provides important insights into the neural basis of mechanical itch, paving the way for developing novel therapies for chronic itch. PERSPECTIVE: Excitatory Nmur2⁺ neurons in the superficial dorsal spinal cord are essential for mechanical but not chemical itch information processing. These spinal Nmur2⁺ neurons represent a potential cellular target for future therapeutic interventions against chronic itch. Spinal and supraspinal Nmur2⁺ neurons may play different roles in pain signal processing.

2024-06-13·ACS Medicinal Chemistry Letters

Discovery of a Pentapeptide Antagonist to Human Neuromedin U Receptor 1

Article

作者: Takayama, Kentaro ; Taniguchi, Atsuhiko ; Hayashi, Yoshio ; Taguchi, Akihiro ; Mori, Kenji ; Sasaki, Yu ; Miyazato, Mikiya

Neuromedin U (NMU) activates two types of receptors (NMUR1 and NMUR2), and the former is mainly expressed in the peripheral tissues, including the intestinal tract and lung tissues. Since NMUR1 contributes to the promotion of type 2 inflammation in these tissues, it is a potential target to suppress inflammatory responses. However, promising antagonist candidates for human NMUR1 have not yet been developed. Here we successfully identified pentapeptide antagonist 9a through a structure-activity relationship study based on hexapeptide lead 1. Its antagonistic activity against human NMUR1 was 10 times greater than that against NMUR2. This is a breakthrough in the development of NMUR1-selective antagonists. Although 9a was relatively stable in the plasma, the C-terminal amide was rapidly degraded to the carboxylic acid by the serum endopeptidase thrombin, which acted as an amidase. This basic information would aid in sample handling in future biological evaluations.

2024-03-14·ACS Medicinal Chemistry Letters

Suppressive Effects of Neuromedin U Receptor 2-Selective Peptide Agonists on Appetite and Prolactin Secretion in Mice

Article

作者: Nagasawa, Kazuki ; Takayama, Kentaro ; Morito, Katsuya ; Suzuki, Yui ; Nomoto, Asuka

Neuromedin U receptor 2 (NMUR2), which is expressed in the central nervous system (CNS) including the hypothalamus, has been noted as a therapeutic target against obesity. We previously reported that intranasal administration of CPN-219, a NMUR2-selective hexapeptide agonist, suppresses body weight gain in mice; however, there is no detailed information regarding its CNS effects. Recently, in addition to appetite suppression, stress responses and regulation of prolactin (PRL) secretion have also attracted attention. NMUR2 expressed in the hypothalamic tuberoinfundibular dopaminergic neurons has emerged as an alternative target for treating hyperprolactinemia. Here, CPN-219 decreased food intake up to 24 h after administration at a dose of 200 nmol, resulting in body weight gain suppression, although grooming and anxiety-like behaviors were transiently induced. Interestingly, the restraint stress-induced increase in plasma PRL levels was significantly suppressed at a lower dose of 20 nmol, indicating the potential for drug development as an anti-PRL agent of NMUR2-selective agonists.