ArticleMolecular pharmacology2013
Pharmacology and structure of isolated conformations of the adenosine A₂A receptor define ligand efficacy.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Article
- Molecular and Structural Insight into Adenosine AMolecular neurobiology · 2023Review
- Sub-millisecond conformational dynamics of the ACommunications biology · 2023Article
- AInternational review of neurobiology · 2023Article
- New fused pyrroles with rA1/A2A antagonistic activity as potential therapeutics for neurodegenerative disorders.Molecular diversity · 2022Article
- Cancer-Associated Mutations of the Adenosine AMolecules (Basel, Switzerland) · 2022Article
- Single Stabilizing Point Mutation Enables High-Resolution Co-Crystal Structures of the Adenosine AAngewandte Chemie (International ed. in English) · 2022Article
- 4-Heteroaryl Substituted Amino-3,5-Dicyanopyridines as New Adenosine Receptor Ligands: Novel Insights on Structure-Activity Relationships and Perspectives.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- Brain Iron Deficiency Changes the Stoichiometry of Adenosine Receptor Subtypes in Cortico-Striatal Terminals: Implications for Restless Legs Syndrome.Molecules (Basel, Switzerland) · 2022Article
- Ligand modulation of the conformational dynamics of the AScientific reports · 2021Article
- Potent and selective ARSC medicinal chemistry · 2021Article
- The Specificity of Downstream Signaling for ABiomedicines · 2020Article
- Ligand-induced conformational changes in a SMALP-encapsulated GPCR.Biochimica et biophysica acta. Biomembranes · 2020Article
- Allosteric Antagonism of the ACells · 2020Article
- Article
- Protein-peptide association kinetics beyond the seconds timescale from atomistic simulations.Nature communications · 2017Article
- ASLAS discovery : advancing life sciences R & D · 2017Article
- A mutagenesis and screening strategy to generate optimally thermostabilized membrane proteins for structural studies.Nature protocols · 2016Article
- From G Protein-coupled Receptor Structure Resolution to Rational Drug Design.The Journal of biological chemistry · 2015Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Using isolated receptor conformations crystal structures of the adenosine A₂A receptor have been solved in active and inactive states. Studying the change in affinity of ligands at these conformations allowed qualitative prediction of compound efficacy in vitro in a system-independent manner. Agonist 5'-N-ethylcarboxamidoadenosine displayed a clear preference to bind to the active state receptor; inverse agonists (xanthine amine congener, ZM241385, SCH58261, and preladenant) bound preferentially to the inactive state, whereas neutral antagonists (theophylline, caffeine, and istradefylline) demonstrated equal affinity for active and inactive states. Ligand docking into the known crystal structures of the A₂A receptor rationalized the pharmacology observed; inverse agonists, unlike neutral antagonists, cannot be accommodated within the agonist-binding site of the receptor. The availability of isolated receptor conformations opens the door to the concept of "reverse pharmacology" whereby the functional pharmacology of ligands can be characterized in a system-independent manner by their affinity for a pair (or set) of G protein-coupled receptor conformations.
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