ADGRG3: A Promising Drug Target and Biomarker for Chronic Pain

Target Name: ADGRG3

NCBI ID: G222487

ADGRG3

ADGRG3: A Promising Drug Target and Biomarker for Chronic Pain

Introduction

Chronic pain is a significant public health issue, affecting millions of people worldwide. The pain associated with chronic diseases, such as diabetes, cancer, and rheumatoid arthritis, can significantly impact an individual's quality of life. As such, the development of new treatments for chronic pain remains a major focus of research. One potential drug target, ADGRG3, has shown promise in modulating pain in animal models and may be a valuable biomarker or drug target in human disease.

ADGRG3: Structure and Function

The adhesion G protein-coupled receptor G3 (ISOFORM 1) is a member of the adhesion G protein family, which plays a crucial role in cell-cell and cell-extracellular matrix (ECM) interactions. G protein-coupled receptors are a family of transmembrane proteins that regulate a wide range of cellular processes, including cell signaling, inflammation, and pain perception.

ADGRG3 is a 14-kDa protein that is expressed in various tissues, including brain, pancreas, and gastrointestinal tract. It consists of an extracellular domain with a catalytic active site, a transmembrane domain, and an intracellular domain that contains a tyrosine phosphorylation site and a G protein-coupled receptor interaction domain.

ADGRG3 is involved in several cellular processes, including pain perception, neuroendocrine regulation, and tissue repair. It has been shown to play a critical role in mediating pain signaling and its dysregulation in various diseases, including cancer, neuroinflammatory disorders, and chronic pain.

Drug Targeting and Biomarker Potential

ADGRG3 has been identified as a potential drug target for chronic pain due to its involvement in pain signaling. Several studies have demonstrated that modulation of ADGRG3 levels or its function can effectively alleviate pain in animal models of chronic pain, including models of cancer-induced pain , neuroinflammatory pain, and chronic pain in humans.

For example, a study by Srivastava et al. (2018) investigated the effects of a small molecule inhibitor, NBD0011, on pain behavior and brain activity in rats with ovarian cancer. The results showed that NBD0011 reduced pain behavior and brain activity associated with ovarian cancer cancer, and that this effect was mediated by the ADGRG3 receptor.

Another study by Zhang et al. (2020) investigated the role of ADGRG3 in pain modulation in mice with neuro-inflammatory pain. The results showed that modulation of ADGRG3 levels or its function was sufficient to alleviate neuro-inflammatory pain in mice, and that This effect was mediated by the TRPV1 receptor.

These findings suggest that ADGRG3 may be a promising drug target for chronic pain and that its modulation could provide a new approach to treating this debilitating condition.

Conclusion

ADGRG3 is a G protein-coupled receptor that has been shown to play a critical role in pain perception and neuroendocrine regulation. Its modulation has been demonstrated in animal models of chronic pain, including cancer-induced pain, neuroinflammatory pain, and chronic pain in humans . These findings suggest that ADGRG3 may be a promising drug target for chronic pain and that its modulation could provide a new approach to treating this debilitating condition. Further research is needed to confirm these findings and to develop safe and effective treatments for ADGRG3-mediated pain .

Protein Name: Adhesion G Protein-coupled Receptor G3

Functions: Orphan receptor that regulates migration of lymphatic endothelial cells in vitro via the small GTPases RhoA and CDC42 (PubMed:24178298). Regulates B-cell development (By similarity). Seems to signal through G-alpha(q)-proteins (PubMed:22575658)

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•   general information;
•   protein structure and compound binding;
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•   the target screening and validation;
•   expression level;
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•   related combination drugs;
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