ArticlePloS one2014
Structural probing of off-target G protein-coupled receptor activities within a series of adenosine/adenine congeners.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
20 citing papers in PubMed, 24 citations in OpenAlex.
- Binding affinities for histamine receptors 1 to 4: Systematic comparison of ligands from the Psychoactive Drug Screening Program KMolecular pharmacology · 2026Review
- Comparative analysis of ligand binding affinities and functional profiles at recombinant human β-adrenergic receptor subtypes 1, 2, and 3.The Journal of pharmacology and experimental therapeutics · 2026Review
- The dual GLP-1 and GIP receptor agonist tirzapetide provides an unintended interaction with the β-adrenoceptors and plays a role in glucose metabolism in hyperglycemic or senescent cardiac cells.Cardiovascular diabetology · 2025Article
- Potent and Selective Human 5-HTJournal of medicinal chemistry · 2024Article
- Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native APurinergic signalling · 2024Article
- Molecular and cellular basis of praziquantel action in the cardiovascular system.American journal of physiology. Cell physiology · 2023Article
- Experimental and In Silico Analysis of Cordycepin and its Derivatives as Endometrial Cancer Treatment.Oncology research · 2019Article
- Article
- Article
- Polypharmacology of conformationally locked methanocarba nucleosides.Drug discovery today · 2017Review
- Factors influencing biased agonism in recombinant cells expressing the human αBritish journal of pharmacology · 2017Article
- Scaffold Repurposing of Nucleosides (Adenosine Receptor Agonists): Enhanced Activity at the Human Dopamine and Norepinephrine Sodium Symporters.Journal of medicinal chemistry · 2017Article
- Structure-Based Scaffold Repurposing for G Protein-Coupled Receptors: Transformation of Adenosine Derivatives into 5HTJournal of medicinal chemistry · 2016Article
- Rigid Adenine Nucleoside Derivatives as Novel Modulators of the Human Sodium Symporters for Dopamine and Norepinephrine.The Journal of pharmacology and experimental therapeutics · 2016Article
- Efficient, large-scale synthesis and preclinical studies of MRS5698, a highly selective A3 adenosine receptor agonist that protects against chronic neuropathic pain.Purinergic signalling · 2015Article
- Engagement of the GABA to KCC2 signaling pathway contributes to the analgesic effects of A3AR agonists in neuropathic pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- John Daly Lecture: Structure-guided Drug Design for Adenosine and P2Y Receptors.Computational and structural biotechnology journal · 2015Review
- In vivo phenotypic screening for treating chronic neuropathic pain: modification of C2-arylethynyl group of conformationally constrained A3 adenosine receptor agonists.Journal of medicinal chemistry · 2014Article
- Computational studies to predict or explain G protein coupled receptor polypharmacology.Trends in pharmacological sciences · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
We studied patterns of off-target receptor interactions, mostly at G protein-coupled receptors (GPCRs) in the µM range, of nucleoside derivatives that are highly engineered for nM interaction with adenosine receptors (ARs). Because of the considerable interest of using AR ligands for treating diseases of the CNS, we used the Psychoactive Drug Screening Program (PDSP) for probing promiscuity of these adenosine/adenine congeners at 41 diverse receptors, channels and a transporter. The step-wise truncation of rigidified, trisubstituted (at N6, C2, and 5' positions) nucleosides revealed unanticipated interactions mainly with biogenic amine receptors, such as adrenergic receptors and serotonergic receptors, with affinities as high as 61 nM. The unmasking of consistent sets of structure activity relationship (SAR) at novel sites suggested similarities between receptor families in molecular recognition. Extensive molecular modeling of the GPCRs affected suggested binding modes of the ligands that supported the patterns of SAR at individual receptors. In some cases, the ligand docking mode closely resembled AR binding and in other cases the ligand assumed different orientations. The recognition patterns for different GPCRs were clustered according to which substituent groups were tolerated and explained in light of the complementarity with the receptor binding site. Thus, some likely off-target interactions, a concern for secondary drug effects, can be predicted for analogues of this set of substructures, aiding the design of additional structural analogues that either eliminate or accentuate certain off-target activities. Moreover, similar analyses could be performed for unrelated structural families for other GPCRs.
Indexed as
Identifiers
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.