ReviewMolecular pharmacology2015
Fulfilling the Promise of "Biased" G Protein-Coupled Receptor Agonism.
Review in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 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
100 citing papers in PubMed.
- Structural basis of PTH1R-β-arrestin core engagement reveals design principles for G-protein-biased therapeutics.Nature structural & molecular biology · 2026Article
- GPCR systems coordinate cellular resilience against aging-associated stress.Frontiers in molecular biosciences · 2026Review
- Biased agonism in psychopharmacology: an opportunity to improve efficacy and safety of treatments.CNS spectrums · 2025Review
- Intracellular GPCR modulators enable precision pharmacology.npj drug discovery · 2025Review
- Design, Synthesis, andACS pharmacology & translational science · 2024Article
- A critical re-evaluation of the slope factor of the operational model of agonism: When to exponentiate operational efficacy.Scientific reports · 2023Article
- Review
- Approved Anti-Obesity Medications in 2022 KSSO Guidelines and the Promise of Phase 3 Clinical Trials: Anti-Obesity Drugs in the Sky and on the Horizon.Journal of obesity & metabolic syndrome · 2023Review
- GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process.International journal of molecular sciences · 2023Article
- Review
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors.Science (New York, N.Y.) · 2023Article
- Biased agonists differentially modulate the receptor conformation ensembles in Angiotensin II type 1 receptor.Journal of molecular graphics & modelling · 2023Article
- Intersection of the Orphan G Protein-Coupled Receptor, GPR19, with the Aging Process.International journal of molecular sciences · 2022Review
- The Pharmacological Effects of Phenylephrine are Indirect, Mediated by Noradrenaline Release from the Cytoplasm.Neurochemical research · 2022Article
- Characterization of recent non-fentanyl synthetic opioids via three different in vitro µ-opioid receptor activation assays.Archives of toxicology · 2022Article
- Saccharin Stimulates Insulin Secretion Dependent on Sweet Taste Receptor-Induced Activation of PLC Signaling Axis.Biomedicines · 2022Article
- Potential therapeutic targets for the treatment of opioid abuse and pain.Advances in pharmacology (San Diego, Calif.) · 2022Review
- Agonist-Promoted Phosphorylation and Internalization of the Kappa Opioid Receptor in Mouse Brains: Lack of Connection With Conditioned Place Aversion.Frontiers in pharmacology · 2022Article
- Proteolytic Cleavage of the Extracellular Domain Affects Signaling of Parathyroid Hormone 1 Receptor.Frontiers in endocrinology · 2022Article
- Agonist-promoted kappa opioid receptor (KOR) phosphorylation has behavioral endpoint-dependent and sex-specific effects.Neuropharmacology · 2022Article
40 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
The fact that over 30% of current pharmaceuticals target heptahelical G protein-coupled receptors (GPCRs) attests to their tractability as drug targets. Although GPCR drug development has traditionally focused on conventional agonists and antagonists, the growing appreciation that GPCRs mediate physiologically relevant effects via both G protein and non-G protein effectors has prompted the search for ligands that can "bias" downstream signaling in favor of one or the other process. Biased ligands are novel entities with distinct signaling profiles dictated by ligand structure, and the potential prospect of biased ligands as better drugs has been pleonastically proclaimed. Indeed, preclinical proof-of-concept studies have demonstrated that both G protein and arrestin pathway-selective ligands can promote beneficial effects in vivo while simultaneously antagonizing deleterious ones. But along with opportunity comes added complexity and new challenges for drug discovery. If ligands can be biased, then ligand classification becomes assay dependent, and more nuanced screening approaches are needed to capture ligand efficacy across several dimensions of signaling. Moreover, because the signaling repertoire of biased ligands differs from that of the native agonist, unpredicted responses may arise in vivo as these unbalanced signals propagate. For any given GPCR target, establishing a framework relating in vitro efficacy to in vivo biologic response is crucial to biased drug discovery. This review discusses approaches to describing ligand efficacy in vitro, translating ligand bias into biologic response, and developing a systems-level understanding of biased agonism in vivo, with the overall goal of overcoming current barriers to developing biased GPCR therapeutics.
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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.