ArticlePurinergic signalling2013
Functional selectivity of adenosine A1 receptor ligands?
Article in Purinergic signalling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- From empirical screening to lipid trolling: the evolution of extrahelical allosteric modulators of AMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- Investigation of adenosine A1 receptor-mediated β-arrestin 2 recruitment using a split-luciferase assay.Frontiers in pharmacology · 2023Article
- International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update.Pharmacological reviews · 2022Review
- Molecular Simulations and Drug Discovery of Adenosine Receptors.Molecules (Basel, Switzerland) · 2022Review
- Novel positive allosteric modulators of AJournal of enzyme inhibition and medicinal chemistry · 2021Article
- Label-free detection of transporter activity via GPCR signalling in living cells: A case for SLC29A1, the equilibrative nucleoside transporter 1.Scientific reports · 2019Article
- New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism.British journal of pharmacology · 2018Review
- Exploring Adenosine Receptor Ligands: Potential Role in the Treatment of Cardiovascular Diseases.Molecules (Basel, Switzerland) · 2017Review
- Structure-Activity Analysis of Biased Agonism at the Human Adenosine A3 Receptor.Molecular pharmacology · 2016Article
- Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Allosteric interactions at adenosine A(1) and A(3) receptors: new insights into the role of small molecules and receptor dimerization.British journal of pharmacology · 2014Review
- Efficacy and ligand bias at the μ-opioid receptor.British journal of pharmacology · 2013Review
- Tissue-nonspecific alkaline phosphatase acts redundantly with PAP and NT5E to generate adenosine in the dorsal spinal cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Adenosine receptors as drug targets--what are the challenges?Nature reviews. Drug discovery · 2013Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The concept of functional selectivity offers great potential for the development of drugs that selectively activate a specific intracellular signaling pathway. During the last few years, it has become possible to systematically analyse compound libraries on G protein-coupled receptors (GPCRs) for this 'biased' form of signaling. We screened over 800 compounds targeting the class of adenosine A(1) receptors using a β-arrestin-mediated signaling assay in U2OS cells as a G protein-independent readout for GPCR activation. A selection of compounds was further analysed in a G protein-mediated GTPγS assay. Additionally, receptor affinity of these compounds was determined in a radioligand binding assay with the agonist [(3)H]CCPA. Of all compounds tested, only LUF5589 9 might be considered as functionally selective for the G protein-dependent pathway, particularly in view of a likely overestimation of β-arrestin signaling in the U2OS cells. Altogether, our study shows that functionally selective ligands for the adenosine A(1) receptor are rare, if existing at all. A thorough analysis of biased signaling on other GPCRs also reveals that only very few compounds can be considered functionally selective. This might indicate that the concept of functional selectivity is less common than speculated.
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