ArticleTrends in pharmacological sciences2014
Computational studies to predict or explain G protein coupled receptor polypharmacology.
Article in Trends in pharmacological sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 31 citations in OpenAlex.
- Activity Models of Key GPCR Families in the Central Nervous System: A Tool for Many Purposes.Journal of chemical information and modeling · 2023Article
- Prediction of dynamic allostery for the transmembrane domain of the sweet taste receptor subunit, TAS1R3.Communications biology · 2023Article
- The Many Faces of G Protein-Coupled Receptor 143, an Atypical Intracellular Receptor.Frontiers in molecular biosciences · 2022Review
- Class A and C GPCR Dimers in Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- G-Protein coupled receptors: structure and function in drug discovery.RSC advances · 2020Review
- Structural insights into emergent signaling modes of G protein-coupled receptors.The Journal of biological chemistry · 2020Review
- Common activation mechanism of class A GPCRs.eLife · 2019Article
- Docking Screens for Dual Inhibitors of Disparate Drug Targets for Parkinson's Disease.Journal of medicinal chemistry · 2018Article
- 5-HTCell · 2018Article
- Exploring G Protein-Coupled Receptors (GPCRs) Ligand Space via Cheminformatics Approaches: Impact on Rational Drug Design.Frontiers in pharmacology · 2018Review
- Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug Design.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Polypharmacology of conformationally locked methanocarba nucleosides.Drug discovery today · 2017Review
- Structure-Based Scaffold Repurposing for G Protein-Coupled Receptors: Transformation of Adenosine Derivatives into 5HTJournal of medicinal chemistry · 2016Article
- In silico prediction of chemical mechanism of action via an improved network-based inference method.British journal of pharmacology · 2016Article
- Structural signatures of DRD4 mutants revealed using molecular dynamics simulations: Implications for drug targeting.Journal of molecular modeling · 2016Article
- New paradigms in GPCR drug discovery.Biochemical pharmacology · 2015Review
- A Key Opinion Leader interview: insight into the research and career of Dr KA Jacobson.Expert opinion on therapeutic patents · 2015Article
- Computational polypharmacology comes of age.Frontiers in pharmacology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Since G protein-coupled receptors (GPCRs) belong to a very large superfamily of evolutionarily related receptors (>800 members in humans), and due to the rapid progress on their structural biology, they are ideal candidates for polypharmacology studies. Broad screening and bioinformatics/chemoinformatics have been applied to understanding off-target effects of GPCR ligands. It is now feasible to approach the question of GPCR polypharmacology using molecular modeling and the available X-ray GPCR structures. As an example, large and sterically constrained adenosine derivatives (potent adenosine receptor ligands with low conformational freedom and multiple extended substituents) were screened for binding at diverse receptors. Unanticipated off-target interactions, including at biogenic amine receptors, were then modeled using a structure-based approach to provide a consistent understanding of recognition. A conserved Asp in TM3 changed its role from counterion for biogenic amines to characteristic H-bonding to adenosine. The same systematic approach could potentially be applied to many GPCRs or other receptors using other sets of congeneric ligands.
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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.