ReviewPharmacology & therapeutics2020
Biased GPCR signaling: Possible mechanisms and inherent limitations.
Review in Pharmacology & therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 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
60 citing papers in PubMed, 112 citations in OpenAlex.
- Arrestins as programmable integrators of GPCR signaling: structural microstates, spatiotemporal logic, and therapeutic control.Cell discovery · 2026Review
- G protein-coupled receptor-mediated platelet thrombus formation.Current opinion in hematology · 2026Review
- Structural dynamics of kappa opioid receptor interactions with β-arrestin 1.Nature communications · 2026Article
- Cytoplasmic tail diversity determines the effector bias of the adhesion GPCR ADGRL2.Cell chemical biology · 2026Article
- ABEL-FRET bridges the timescale gap in single-molecule measurements of the structural dynamics in the ACommunications chemistry · 2026Article
- Molecular determinants of signal transduction in tropomyosin receptor kinases.FEBS open bio · 2026Review
- Cytoplasmic tail composition modulates the G protein and arrestin-3 signaling bias of the adhesion GPCR LPHN2.bioRxiv : the preprint server for biology · 2025Article
- G-protein coupled receptors in metabolic reprogramming and cancer.Pharmacology & therapeutics · 2025Review
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- How Ligands Achieve Biased Signaling toward Arrestins.Biochemistry · 2025Review
- Emerging paradigms for target discovery of traditional medicines: A genome-wide pan-GPCR perspective.Innovation (Cambridge (Mass.)) · 2025Review
- Effects of positive mGlu5 modulation on DJournal of psychopharmacology (Oxford, England) · 2025Article
- Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches.Molecules (Basel, Switzerland) · 2025Review
- Higher-order transient membrane protein structures.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Disease-Associated Dopamine Receptor D2 Variants Exhibit Functional Consequences Depending on Different Heterotrimeric G-Protein Subunit Combinations.Biomedicines · 2024Article
- Minute-timescale free-energy calculations reveal a pseudo-active state in the adenosine AChem · 2024Article
- Carvedilol Activates a Myofilament Signaling Circuitry to Restore Cardiac Contractility in Heart Failure.JACC. Basic to translational science · 2024Article
- GRK specificity and Gβγ dependency determines the potential of a GPCR for arrestin-biased agonism.Communications biology · 2024Article
- GPCR-dependent and -independent arrestin signaling.Trends in pharmacological sciences · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptors (GPCRs) are targeted by about a third of clinically used drugs. Many GPCRs couple to more than one type of heterotrimeric G proteins, become phosphorylated by any of several different GRKs, and then bind one or more types of arrestin. Thus, classical therapeutically active drugs simultaneously initiate several branches of signaling, some of which are beneficial, whereas others result in unwanted on-target side effects. The development of novel compounds to selectively channel the signaling into the desired direction has the potential to become a breakthrough in health care. However, there are natural and technological hurdles that must be overcome. The fact that most GPCRs are subject to homologous desensitization, where the active receptor couples to G proteins, is phosphorylated by GRKs, and then binds arrestins, suggest that in most cases the GPCR conformations that facilitate their interactions with these three classes of binding partners significantly overlap. Thus, while partner-specific conformations might exist, they are likely low-probability states. GPCRs are inherently flexible, which suggests that complete bias is highly unlikely to be feasible: in the conformational ensemble induced by any ligand, there would be some conformations facilitating receptor coupling to unwanted partners. Things are further complicated by the fact that virtually every cell expresses numerous G proteins, several GRK subtypes, and two non-visual arrestins with distinct signaling capabilities. Finally, novel screening methods for measuring ligand bias must be devised, as the existing methods are not specific for one particular branch of signaling.
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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.