Evidence mapPaperPMID 39747671Full record

ReviewNature reviews. Drug discovery2025

Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.

Paolo Conflitti, Edward Lyman, Mark S P Sansom, Peter W Hildebrand, Hugo Gutiérrez-de-Terán, Paolo Carloni, T Bertie Ansell, Shuguang Yuan, Patrick Barth, Anne S Robinson and 6 more

Abstract readReview
In one paragraph

Review in Nature reviews. Drug discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. A BBB-permeable βScience advances · 2026
    Article
  9. Article
  10. Article
  11. Structural Mechanism of an Efficacy Photoswitch Targeting the βAngewandte Chemie (International ed. in English) · 2026
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Paolo ConflittiEuler Institute, Faculty of Biomedical Sciences, Università della Svizzera italiana (USI), Lugano, Switzerland.ORCID 0000-0002-5440-6167
Edward LymanDepartment of Physics and Astronomy, University of Delaware, Newark, DE, USA.ORCID 0000-0003-4590-0363
Mark S P SansomDepartment of Biochemistry, University of Oxford, Oxford, UK.ORCID 0000-0001-6360-7959
Peter W HildebrandInstitute of Medical Physics and Biophysics, Faculty of Medicine, Leipzig University, Leipzig, Germany.ORCID 0000-0003-0063-1104
Hugo Gutiérrez-de-TeránDepartment of Cell and Molecular Biology, Uppsala University, Biomedical Centre, Uppsala, Sweden.ORCID 0000-0003-0459-3491
Paolo CarloniINM-9/IAS-5 Computational Biomedicine, Forschungszentrum Jülich, Jülich, Germany.
T Bertie AnsellDepartment of Biochemistry, University of Oxford, Oxford, UK.
Shuguang YuanInstitute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.ORCID 0000-0001-9858-4742
Patrick BarthInterfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.ORCID 0000-0002-0744-6844
Anne S RobinsonDepartment of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.ORCID 0000-0001-7235-1481
Christopher G TateMRC Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0002-2008-9183
David GloriamDepartment of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark.ORCID 0000-0002-4299-7561
Stephan GrzesiekFocal Area Structural Biology and Biophysics, Biozentrum, University of Basel, Basel, Switzerland.ORCID 0000-0003-1998-4225
Matthew T EddyDepartment of Chemistry, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-3349-6212
Scott ProsserDepartment of Chemistry, University of Toronto, Mississauga, Ontario, Canada.
Vittorio LimongelliEuler Institute, Faculty of Biomedical Sciences, Università della Svizzera italiana (USI), Lugano, Switzerland. vittoriolimongelli@gmail.com.ORCID 0000-0002-4861-1199

Funding

Supplemental Postdoc: Lipid dependent GPCR signaling: Thermodynamics and mechanismsR35GM153273 · UNIVERSITY OF DELAWARE · 2025 to 2025
$559k
NIGMS NIH HHS R35 GM138291NIGMS NIH HHS R35 GM153273
6 · The paper itself

Abstract

G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors. Recent advances in X-ray crystallography, cryo-electron microscopy, spectroscopic techniques and molecular simulations have enhanced our understanding of receptor conformational dynamics and ligand interactions with GPCRs. These developments have revealed novel ligand-binding modes, mechanisms of action and druggable pockets. In this Review, we highlight such aspects for recently discovered small-molecule drugs and drug candidates targeting GPCRs, focusing on three categories: allosteric modulators, biased ligands, and bivalent and bitopic compounds. Although studies so far have largely been retrospective, integrating structural data on ligand-induced receptor functional dynamics into the drug discovery pipeline has the potential to guide the identification of drug candidates with specific abilities to modulate GPCR interactions with intracellular effector proteins such as G proteins and β-arrestins, enabling more tailored selectivity and efficacy profiles.

Indexed as

Drug DiscoveryReceptors, G-Protein-CoupledAllosteric RegulationAnimalsHumansLigandsLigandsReceptors, G-Protein-Coupled

Identifiers

PMID39747671
PMCPMC11968245

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.