ReviewMolecular endocrinology (Baltimore, Md.)2014
Minireview: More than just a hammer: ligand "bias" and pharmaceutical discovery.
Review in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 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
67 citing papers in PubMed, 127 citations in OpenAlex.
- Investigation into ligand selectivity and bias at the formyl peptide receptor family.The Journal of pharmacology and experimental therapeutics · 2026Article
- Review
- Biased Signaling and Its Role in the Genesis of Short- and Long-Acting βBiochemistry · 2025Article
- Multiple intramolecular triggers converge to preferential G protein coupling in the CBNature communications · 2025Article
- Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches.Molecules (Basel, Switzerland) · 2025Review
- Article
- Assessment of the potential of novel and classical opioids to induce respiratory depression in mice.British journal of pharmacology · 2023Article
- Quantitative assessment of ligand bias from bias plots: The bias coefficient "kappa".Biochimica et biophysica acta. General subjects · 2023Article
- Structure-function relationship and physiological role of apelin and its G protein coupled receptor.Biophysical reviews · 2023Review
- Quantitative receptor model for responses that are left- or right-shifted versus occupancy (are more or less concentration sensitive): the SABRE approach.Frontiers in pharmacology · 2023Article
- Functional Properties of Two Distinct PTH1R Mutants Associated With Either Skeletal Defects or Pseudohypoparathyroidism.JBMR plus · 2022Article
- Review
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Biased Allosteric Modulators: New Frontiers in GPCR Drug Discovery.Trends in pharmacological sciences · 2021Review
- The Biased Ligands NGF and NT-3 Differentially Stabilize Trk-A Dimers.Biophysical journal · 2021Article
- Inhibitory signaling in mammalian olfactory transduction potentially mediated by GαMolecular and cellular neurosciences · 2021Article
- Ligand bias in receptor tyrosine kinase signaling.The Journal of biological chemistry · 2020Review
- Beta-arrestins operate an on/off control switch for focal adhesion kinase activity.Cellular and molecular life sciences : CMLS · 2020Article
- Position Review: Functional Selectivity in Mammalian Olfactory Receptors.Chemical senses · 2020Review
- A single unified model for fitting simple to complex receptor response data.Scientific reports · 2020Article
7 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
1 author at 1 institution in 1 country.
Funding
Abstract
Conventional orthosteric drug development programs targeting G protein-coupled receptors (GPCRs) have focused on the concepts of agonism and antagonism, in which receptor structure determines the nature of the downstream signal and ligand efficacy determines its intensity. Over the past decade, the emerging paradigms of "pluridimensional efficacy" and "functional selectivity" have revealed that GPCR signaling is not monolithic, and that ligand structure can "bias" signal output by stabilizing active receptor states in different proportions than the native ligand. Biased ligands are novel pharmacologic entities that possess the unique ability to qualitatively change GPCR signaling, in effect creating "new receptors" with distinct efficacy profiles driven by ligand structure. The promise of biased agonism lies in this ability to engender "mixed" effects not attainable using conventional agonists or antagonists, promoting therapeutically beneficial signals while antagonizing deleterious ones. Indeed, arrestin pathway-selective agonists for the type 1 parathyroid hormone and angiotensin AT1 receptors, and G protein pathway-selective agonists for the GPR109A nicotinic acid and μ-opioid receptors, have demonstrated unique, and potentially therapeutic, efficacy in cell-based assays and preclinical animal models. Conversely, activating GPCRs in "unnatural" ways may lead to downstream biological consequences that cannot be predicted from prior knowledge of the actions of the native ligand, especially in the case of ligands that selectively activate as-yet poorly characterized G protein-independent signaling networks mediated via arrestins. Although much needs to be done to realize the clinical potential of functional selectivity, biased GPCR ligands nonetheless appear to be important new additions to the pharmacologic toolbox.
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.