ArticleBritish journal of pharmacology2012
Functional efficacy of adenosine A₂A receptor agonists is positively correlated to their receptor residence time.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
- Residence time in drug discovery: current insights and future perspectives.Pharmacological reports : PR · 2025Review
- Intracellular Pocket Conformations Determine Signaling Efficacy through the μ Opioid Receptor.Journal of chemical information and modeling · 2025Article
- Exploring the pharmacological mechanisms for alleviating OSA: Adenosine A2A receptor downregulation of the PI3K/Akt/HIF‑1 pathway (Review).Biomedical reports · 2025Review
- Agonist efficacy at the βFrontiers in pharmacology · 2025Article
- Intracellular pocket conformations determine signaling efficacy through thebioRxiv : the preprint server for biology · 2024Article
- Positive allosteric modulation of a GPCR ternary complex.Science advances · 2024Article
- Know your molecule: pharmacological characterization of drug candidates to enhance efficacy and reduce late-stage attrition.Nature reviews. Drug discovery · 2024Review
- Calculating Protein-Ligand Residence Times through State Predictive Information Bottleneck Based Enhanced Sampling.Journal of chemical theory and computation · 2024Article
- Pseudoirreversible inhibition elicits persistent efficacy of a sphingosine 1-phosphate receptor 1 antagonist.Nature communications · 2024Article
- Structural Modification and Biological Evaluation of 2,8-Disubstituted Adenine and Its Nucleosides as AJournal of medicinal chemistry · 2024Article
- Article
- Calculating Protein-Ligand Residence Times Through State Predictive Information Bottleneck based Enhanced Sampling.bioRxiv : the preprint server for biology · 2024Article
- PaCS-Toolkit: Optimized Software Utilities for Parallel Cascade Selection Molecular Dynamics (PaCS-MD) Simulations and Subsequent Analyses.The journal of physical chemistry. B · 2024Article
- Data-driven classification of ligand unbinding pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Roles of Accelerated Molecular Dynamics Simulations in Predictions of Binding Kinetic Parameters.Mini reviews in medicinal chemistry · 2024Review
- AMolecular pharmacology · 2023Article
- Machine learning methods for developments of binding kinetic models in predicting protein-ligand dissociation rate constants.Smart molecules : open access · 2023Article
- Probing the structure of human tRNARSC advances · 2023Article
- Computational Design of Potent and Selective d-Peptide Agonists of the Glucagon-like Peptide-2 Receptor.Journal of medicinal chemistry · 2023Article
- New paradigms in purinergic receptor ligand discovery.Neuropharmacology · 2023Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND PURPOSE The adenosine A(2A) receptor belongs to the superfamily of GPCRs and is a promising therapeutic target. Traditionally, the discovery of novel agents for the A(2A) receptor has been guided by their affinity for the receptor. This parameter is determined under equilibrium conditions, largely ignoring the kinetic aspects of the ligand-receptor interaction. The aim of this study was to assess the binding kinetics of A(2A) receptor agonists and explore a possible relationship with their functional efficacy. EXPERIMENTAL APPROACH We set up, validated and optimized a kinetic radioligand binding assay (a so-called competition association assay) at the A(2A) receptor from which the binding kinetics of unlabelled ligands were determined. Subsequently, functional efficacies of A(2A) receptor agonists were determined in two different assays: a novel label-free impedance-based assay and a more traditional cAMP determination. KEY RESULTS A simplified competition association assay yielded an accurate determination of the association and dissociation rates of unlabelled A(2A) receptor ligands at their receptor. A correlation was observed between the receptor residence time of A(2A) receptor agonists and their intrinsic efficacies in both functional assays. The affinity of A(2A) receptor agonists was not correlated to their functional efficacy. CONCLUSIONS AND IMPLICATIONS This study indicates that the molecular basis of different agonist efficacies at the A(2A) receptor lies within their different residence times at this receptor.
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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.