ArticleNature communications2016
The role of kinetic context in apparent biased agonism at GPCRs.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 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
185 citing papers in PubMed.
- Next-Generation GLP-1 Agonist Bioassays: Integrating Precision with Biological Relevance.International journal of molecular sciences · 2026Article
- Steric control of signaling bias in the immunometabolic receptor GPR84.Nature communications · 2026Article
- Spatiotemporal modeling of GPCR signaling: The role of endosomal dynamics and receptor recycling.PLoS computational biology · 2026Article
- The structure of the dopamine DScience advances · 2026Article
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Hold on tight: the kinetic profiling of opioid receptor ligands using the CORAL-MD.Journal of cheminformatics · 2026Article
- From Antipsychotic to Antitumor Agent: Cariprazine Suppresses Glioblastoma via D2/D3-ARRB2 Axis Modulation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Dynamic Pathway Selectivity of TAS2R5 toward or Away from β-Arrestin or G Protein from Biased Agonists.Biochemistry · 2026Article
- Agonism and Biased Signaling.Handbook of experimental pharmacology · 2026Review
- The ABCs of psychedelics: a preclinical roadmap for drug discovery.Trends in pharmacological sciences · 2025Review
- Biased Orthosteric Agonism and Allosteric Modulation: Emerging Strategies for Developing New Class of β-Agonists for Obstructive Airway Diseases.American journal of respiratory cell and molecular biology · 2025Review
- Transient ligand contacts of the intrinsically disordered N-terminus of neuropeptide YNature communications · 2025Article
- Efficient Characterization of GPCRs Allosteric Modulation: Application to the Rational Design of De Novo S1PR1 Allosteric Modulators.Journal of chemical information and modeling · 2025Article
- Biased Signaling and Its Role in the Genesis of Short- and Long-Acting βBiochemistry · 2025Article
- Discrete spatiotemporal encoding of striatal dopamine transmission.Science (New York, N.Y.) · 2025Article
- Identification of a Lipid-Exposed Extrahelical Binding Site for Positive Allosteric Modulators of the Dopamine DACS chemical neuroscience · 2025Article
- Prolonged signaling of backbone-modified glucagon-like peptide-Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Smooth operator(s): dialing up and down neurotransmitter responses by G-protein regulators.Trends in cell biology · 2025Review
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- The structural diversity of psychedelic drug actions revealed.Nature communications · 2025Article
125 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that 'kinetic context', as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism.
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.