更新于：2024-11-01

GPR27

更新于：2024-11-01

基本信息

别名

G protein-coupled receptor 27、GPR27、Probable G-protein coupled receptor 27

+ [2]

简介

Orphan receptor. Possible candidate for amine-like G-protein coupled receptor.

关联

项与 GPR27 相关的药物

PT-91

靶点

GPR27

作用机制

GPR27调节剂

在研机构

University of Liege

原研机构

University of Liege

在研适应症

糖尿病

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 GPR27 相关的临床结果

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100 项与 GPR27 相关的转化医学

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0 项与 GPR27 相关的专利（医药）

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项与 GPR27 相关的文献（医药）

2023-12-28·Journal of Medicinal Chemistry1区 · 医学

Development of Ligands for the Super Conserved Orphan G Protein-Coupled Receptor GPR27 with Improved Efficacy and Potency

1区 · 医学

Article

作者: Hanson, Julien ; Laufer, Stefan A ; Pillaiyar, Thanigaimalai ; Stäubert, Claudia ; Kronenberger, Thales ; Poso, Antti ; Liebing, Aenne-Dorothea ; Abboud, Dayana ; Wozniak, Monika ; Rasch, Alexander

The orphan G protein-coupled receptor GPR27 appears to play a role in insulin production, secretion, lipid metabolism, neuronal plasticity, and l-lactate homeostasis. However, investigations on the function of GPR27 are impaired by the lack of potent and efficacious agonists. We describe herein the development of di- and trisubstituted benzamide derivatives 4a-e, 7a-z, and 7aa-ai, which display GPR27-specific activity in a β-arrestin 2 recruitment-based assay. Highlighted compounds are PT-91 (7p: pEC₅₀ 6.15; E_max 100%) and 7ab (pEC₅₀ 6.56; E_max 99%). A putative binding mode was revealed by the docking studies of 7p and 7ab with a GPR27 homology model. The novel active compounds exhibited no GPR27-mediated activation of G proteins, indicating that the receptor may possess an atypical profile. Compound 7p displays high metabolic stability and brain exposure in mice. Thus, 7p represents a novel tool to investigate the elusive pharmacology of GPR27 and assess its potential as a drug target.

2023-11-01·Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Characterizing the SREB G protein-coupled receptor family in fish: Brain gene expression and genomic differences in upstream transcription factor binding sites

Article

作者: Francis, Mullein ; Patnaude, Michael ; Murray, Casey A ; DiMaggio, Matthew A ; Breton, Timothy S ; Fike, Samantha

The SREB (Super-conserved Receptors Expressed in Brain) family of orphan G protein-coupled receptors is highly conserved in vertebrates and consists of three members: SREB1 (orphan designation GPR27), SREB2 (GPR85), and SREB3 (GPR173). SREBs are associated with processes ranging from neuronal plasticity to reproductive control. Relatively little is known about similarities across the entire family, or how mammalian gene expression patterns compare to non-mammalian vertebrates. In fish, this system may be particularly complex, as some species have gained a fourth member (SREB3B) while others have lost genes. To better understand the system, the present study aimed to: 1) use qPCR to characterize sreb and related gene expression patterns in the brains of three fish species with different systems, and 2) identify possible differences in transcriptional regulation among the receptors, using upstream transcription factor binding sites across 70 ray-finned fish genomes. Overall, regional patterns of sreb expression were abundant in forebrain-related areas. However, some species-specific patterns were detected, such as abundant expression of receptors in zebrafish (Danio rerio) hypothalamic-containing sections, and divergence between sreb3a and sreb3b in pufferfish (Dichotomyctere nigroviridis). In addition, a gene possibly related to the system (dkk3a) was spatially correlated with the receptors in all three species. Genomic regions upstream of sreb2 and sreb3b, but largely not sreb1 or sreb3a, contained many highly conserved transcription factor binding sites. These results provide novel information about expression differences and transcriptional regulation across fish that may inform future research to better understand these receptors.

2023-09-12·Aging

Prognostic significance and immune characteristics of GPR27 in gastric cancer.

Article

作者: Gao, Yuanjun ; Pan, Jun

Gastric cancer (GC) is one of the most typical cancerous neoplasms occurring in the digestive system. For advanced GC, immunotherapy is the final option for them to prolong survival time. Hence, we aimed to identify new molecular targets to enhance the immunotherapy response in GC individuals. Then we applied bioinformatic analysis to explore the expression profiles of G-protein-coupled receptor 27 (GPR27) transcription and GPR27 methylation. The associations between survival of GC patients and GPR27 transcription and methylation were then analyzed. We also studied the link between GPR27 expression and levels of immune cell infiltration. Finally, we gained insights into the prognostic role of GPR27 protein in 97 cases of GC individuals. According to datasets gained from TCGA, GPR27 mRNA is expressed lower in GC tissues. Down-regulation of GPR27 transcription was related with better survival in GC individuals, and GPR27 cg03024619 had the most significant prognostic value (HR=0.553, P<0.0001). In addition, the expression level of GPR27 has a clear interaction with immune cells' infiltration and their markers. Single-cell analysis displayed that GPR27 is mainly expressed in macrophages. Finally, down-regulation of GPR27 protein was observed in GC tissues and correlated with better survival outcomes. GPR27 can serve as an important prognostic biomarker and exert an immunomodulatory role in GC. Our findings highlight the significance of GPR27 in a variety of cancers, including GC, and provide clues for a better understanding of GPR27 from bioinformatics and clinically validated perspective.