更新于：2024-11-01

NMUR2 x NMUR1

更新于：2024-11-01

基本信息

关联

项与 NMUR2 x NMUR1 相关的药物

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

100 项与 NMUR2 x NMUR1 相关的临床结果

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100 项与 NMUR2 x NMUR1 相关的转化医学

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0 项与 NMUR2 x NMUR1 相关的专利（医药）

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项与 NMUR2 x NMUR1 相关的文献（医药）

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.

2023-09-01·Pharmacological Research

The neuromedin U system: Pharmacological implications for the treatment of obesity and binge eating behavior

Review

作者: Botticelli, Luca ; Giorgioni, Gianfabio ; Micioni Di Bonaventura, Maria Vittoria ; Piergentili, Alessandro ; Quaglia, Wilma ; Cifani, Carlo ; Bonifazi, Alessandro ; Micioni Di Bonaventura, Emanuela ; Del Bello, Fabio

Neuromedin U (NMU) is a bioactive peptide produced in the gut and in the brain, with a role in multiple physiological processes. NMU acts by binding and activating two G protein coupled receptors (GPCR), the NMU receptor 1 (NMU-R1), which is predominantly expressed in the periphery, and the NMU receptor 2 (NMU-R2), mainly expressed in the central nervous system (CNS). In the brain, NMU and NMU-R2 are consistently present in the hypothalamus, commonly recognized as the main "feeding center". Considering its distribution pattern, NMU revealed to be an important neuropeptide involved in the regulation of food intake, with a powerful anorexigenic ability. This has been observed through direct administration of NMU and by studies using genetically modified animals, which revealed an obesity phenotype when the NMU gene is deleted. Thus, the development of NMU analogs or NMU-R2 agonists might represent a promising pharmacological strategy to treat obese individuals. Furthermore, NMU has been demonstrated to influence the non-homeostatic aspect of food intake, playing a potential role in binge eating behavior. This review aims to discuss and summarize the current literature linking the NMU system with obesity and binge eating behavior, focusing on the influence of NMU on food intake and the neuronal mechanisms underlying its anti-obesity properties. Pharmacological strategies to improve the pharmacokinetic profile of NMU will also be reported.

2023-01-01·Peptides

Postnatal ontogeny of Neuromedin S and its receptors NMUR1 and NMUR2 expression in mouse testis

Article

作者: Yadav, Anupam ; Rajpoot, Arti ; Mishra, Raghav Kumar ; Yadav, Kiran

Neuromedin S (NMS) is a well-known anorexigenic neuropeptide. Despite some reports of the presence of its transcript and precursor protein in testis, the expression and localization of NMS and its receptors during the postnatal development of mammalian testis remains elusive. We investigated the expression patterns and testicular localization of NMS and its receptors NMUR1 and NMUR2, during 5, 10, 20, 30, and 90 days of postnatal development, using real time PCR, immunoblot analysis and immunohistochemistry in mice. NMS and its receptors are present at all age groups at transcript level in mouse testis. At the protein level, NMS and NMUR2 are present in all age groups, whereas NMUR1 is present primarily in 30- and 90-day testis. Immunolocalization study showed that NMS and NMUR2 are expressed in spermatogonia, spermatocytes, Sertoli cells, and Leydig cells, in contrast to NMUR1 which is expressed exclusively in the Leydig cells of 30- and 90-day testis. The results also confirm the intranuclear localization of NMS in spermatogonia and spermatocytes. Although NMS-NMUR2 is expressed in Sertoli cells at all stages of the spermatogenic cycle, they showed a stage-specific expression pattern in spermatogonia and primary spermatocytes. In conclusion, NMS and its receptors NMUR1 and NMUR2 are expressed in the testis and may regulate spermatogenesis, possibly by modulating steroidogenesis and Sertoli cell function in the testis.