ArticlePloS one2018
Computationally identified novel agonists for GPRC6A.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Osteocalcin binds to a GPRC6A Venus fly trap allosteric site to positively modulate GPRC6A signaling.FASEB bioAdvances · 2024Article
- GPRC6A is a Potential Therapeutic Target for Metformin Regulation of Glucose Homeostasis in Mice.bioRxiv : the preprint server for biology · 2024Article
- Extended-ensemble docking to probe dynamic variation of ligand binding sites during large-scale structural changes of proteins.Chemical science · 2022Article
- Osteocalcin and the physiology of danger.FEBS letters · 2022Review
- Review
- Explaining Divergent Observations Regarding Osteocalcin/GPRC6A Endocrine Signaling.Endocrinology · 2021Review
- Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.Journal of chemical information and modeling · 2020Article
- Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.ChemRxiv : the preprint server for chemistry · 2020Article
- Humanized GPRC6AScientific reports · 2020Article
- Role of GPRC6A in Regulating Hepatic Energy Metabolism in Mice.Scientific reports · 2020Article
- SHBG141-161 Domain-Peptide Stimulates GPRC6A-Mediated Response in Leydig and β-Langerhans cell lines.Scientific reports · 2019Article
- Human GPRC6A Mediates Testosterone-Induced Mitogen-Activated Protein Kinases and mTORC1 Signaling in Prostate Cancer Cells.Molecular pharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
New insights into G protein coupled receptor regulation of glucose metabolism by β-cells, skeletal muscle and liver hepatocytes identify GPRC6A as a potential therapeutic target for treating type 2 diabetes mellitus (T2D). Activating GPRC6A with a small molecule drug represents a potential paradigm-shifting opportunity to make significant strides in regulating glucose homeostasis by simultaneously correcting multiple metabolic derangements that underlie T2D, including abnormalities in β-cell proliferation and insulin secretion and peripheral insulin resistance. Using a computational, structure-based high-throughput screening approach, we identified novel tri-phenyl compounds predicted to bind to the venus fly trap (VFT) and 7-transmembrane (7-TM) domains of GPRC6A. Experimental testing found that these compounds dose-dependently stimulated GPRC6A signaling in a heterologous cell expression system. Additional chemical modifications and functional analysis identified one tri-phenyl lead compound, DJ-V-159 that demonstrated the greatest potency in stimulating insulin secretion in β-cells and lowering serum glucose in wild-type mice. Collectively, these studies show that GPRC6A is a "druggable" target for developing chemical probes to treat T2DM.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.