ReviewBioorganic & medicinal chemistry letters2016
Biased agonism: An emerging paradigm in GPCR drug discovery.
Review in Bioorganic & medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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
147 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Evaluating biased agonism of glucagon-like peptide-1 (GLP-1) receptors to improve cellular bioenergetics: A systematic review.Diabetes, obesity & metabolism · 2025Pooled it
- Comparison of oliceridine and sufentanil in postoperative pain management for postoperative nausea and vomiting after bimaxillary orthognathic surgery: an exploratory randomized controlled trial.Frontiers in medicine · 2026Trial
- Agonist-specific conformational dynamics at the βBritish journal of pharmacology · 2026Article
- Article
- Structural basis of PTH1R-β-arrestin core engagement reveals design principles for G-protein-biased therapeutics.Nature structural & molecular biology · 2026Article
- An engineered nanobody inhibitor for molecular-to-circuit control of opioid receptor function.bioRxiv : the preprint server for biology · 2026Article
- Structural Basis of GPCR-Biased Modulation.Handbook of experimental pharmacology · 2026Review
- Targeting muscarinic receptors for treating schizophrenia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Peptide-based therapeutics targeting GPCRs: recent applications in the treatment of metabolic disorders.Frontiers in pharmacology · 2026Review
- Kappa opioid receptor control of motivated behavior revisited.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Molecular Mechanisms of Depression: The Interplay Between Genes and Receptors.International journal of molecular 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
- Cannabinoid Receptor 2 (CB2) in Macrophages: A Promising Clinical Target for Immune Disorders.International journal of molecular sciences · 2025Review
- Monoclonal Antibody 5F1 Modulates Formyl Peptide Receptor 1 Conformation for Transmembrane Signaling.FASEB bioAdvances · 2025Article
- Biased agonism in psychopharmacology: an opportunity to improve efficacy and safety of treatments.CNS spectrums · 2025Review
- Residence time in drug discovery: current insights and future perspectives.Pharmacological reports : PR · 2025Review
- Expanding Horizons of Buprenorphine: A Comprehensive Narrative Review of Its Pharmacological Properties and Clinical Applications in Chronic Pain.Pain and therapy · 2025Review
- Pharmacological characterization of the novel selective kappa opioid receptor agonists 10-Iodo-Akuammicine and 10-Bromo-akuammicine in mice.Neuropharmacology · 2025Article
- Induced proximity at the cell surface.Nature biotechnology · 2025Review
- Biased antagonism of a series of bicyclic CXCR2 intracellular allosteric modulators.Frontiers in pharmacology · 2025Article
87 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
3 authors.
Funding
Abstract
G protein coupled receptors have historically been one of the most druggable classes of cellular proteins. The members of this large receptor gene family couple to primary effectors, G proteins, that have built in mechanisms for regeneration and amplification of signaling with each engagement of receptor and ligand, a kinetic event in itself. In recent years GPCRs, have been found to interact with arrestin proteins to initiate signal propagation in the absence of G protein interactions. This pinnacle observation has changed a previously held notion of the linear spectrum of GPCR efficacy and uncovered a new paradigm in GPCR research and drug discovery that relies on multidimensionality of GPCR signaling. Ligands were found that selectively confer activity in one pathway over another, and this phenomenon has been referred to as 'biased agonism' or 'functional selectivity'. While great strides in the understanding of this phenomenon have been made in recent years, two critical questions still dominate the field: How can we rationally design biased GPCR ligands, and ultimately, which physiological responses are due to G protein versus arrestin interactions? This review will discuss the current understanding of some of the key aspects of biased signaling that are related to these questions, including mechanistic insights in the nature of biased signaling and methods for measuring ligand bias, as well as relevant examples of drug discovery applications and medicinal chemistry strategies that highlight the challenges and opportunities in this rapidly evolving field.
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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.