ArticleNature communications2016
Structure-guided development of heterodimer-selective GPCR ligands.
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 56 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
56 citing papers in PubMed, 95 citations in OpenAlex.
- Review
- Mechanistic and therapeutic insights into class A GPCR dimers in neuropsychiatric disorders.npj drug discovery · 2026Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Single-molecule characterization of opioid receptor heterodimers reveals soluble µ-δ dimer blocker peptide alleviates morphine tolerance.Nature communications · 2025Article
- Mechanism and function of GPR3 regulated by a negative allosteric modulator.Nature communications · 2025Article
- β2-Adrenergic Receptor Utilizes Distinct Interaction Interfaces to Selectively form Heterooligomers with a Subset of Bitter Taste Receptors.Biochemistry · 2025Article
- Investigation of the Binding Characteristics of Agonists and Various Antagonists Targeting Histamine 1 Receptor.Pharmaceutical research · 2025Article
- In Vitro Signaling Properties of Cannabinoid and Orexin Receptors: How Orexin Receptors Influence Cannabinoid Receptor-Mediated Signaling.Pharmacology research & perspectives · 2025Article
- Design, Synthesis, and Characterization of New δ Opioid Receptor-Selective Fluorescent Probes and Applications in Single-Molecule Microscopy of Wild-Type Receptors.Journal of medicinal chemistry · 2024Article
- The crosstalk between 5-HTNeuropharmacology · 2023Review
- Constrained catecholamines gain βNature communications · 2023Article
- Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor.Nature communications · 2023Article
- Review
- Novel bivalent ligands carrying potential antinociceptive effects by targeting putative mu opioid receptor and chemokine receptor CXCR4 heterodimers.Bioorganic chemistry · 2022Article
- Prediction of molecular interactions and physicochemical properties relevant for vasopressin V2 receptor antagonism.Journal of molecular modeling · 2022Article
- Update on GPCR-based targets for the development of novel antidepressants.Molecular psychiatry · 2022Review
- Mechanistic insight into the impact of a bivalent ligand on the structure and dynamics of a GPCR oligomer.Computational and structural biotechnology journal · 2022Article
- GPCR heteromers: An overview of their classification, function and physiological relevance.Frontiers in endocrinology · 2022Review
- Leveraging nonstructural data to predict structures and affinities of protein-ligand complexes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Functional Selectivity of Dopamine DInternational journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crystal structures of G protein-coupled receptor (GPCR) ligand complexes allow a rational design of novel molecular probes and drugs. Here we report the structure-guided design, chemical synthesis and biological investigations of bivalent ligands for dopamine D2 receptor/neurotensin NTS1 receptor (D2R/NTS1R) heterodimers. The compounds of types 1-3 consist of three different D2R pharmacophores bound to an affinity-generating lipophilic appendage, a polyethylene glycol-based linker and the NTS1R agonist NT(8-13). The bivalent ligands show binding affinity in the picomolar range for cells coexpressing both GPCRs and unprecedented selectivity (up to three orders of magnitude), compared with cells that only express D2Rs. A functional switch is observed for the bivalent ligands 3b,c inhibiting cAMP formation in cells singly expressing D2Rs but stimulating cAMP accumulation in D2R/NTS1R-coexpressing cells. Moreover, the newly synthesized bivalent ligands show a strong, predominantly NTS1R-mediated β-arrestin-2 recruitment at the D2R/NTS1R-coexpressing cells.
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.