Evidence mapPaperPMID 41206221Full record

ReviewTrends in pharmacological sciences2025

Elucidating biased signaling in class A GPCRs.

Ningyang Xu, Edwin Legall, Roger H Johnson, Lan Zhu, Wei Liu

Abstract readReview
In one paragraph

Review in Trends in pharmacological sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

5 authors.

Ningyang XuCancer Center and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Edwin LegallCancer Center and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Roger H JohnsonCancer Center and Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Lan ZhuCancer Center and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: lzhu@mcw.edu.
Wei LiuCancer Center and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: weiliu@mcw.edu.

Funding

Structural Biology of Dopamine SignalingR01GM140078 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI Wei Liu · 2022 to 2024
$640k
Structural Dynamics of GPCR Oligomerization: Impact on Localization and SignalingR35GM159978 · MEDICAL COLLEGE OF WISCONSIN · 2025 to 2025
$390k
NIGMS NIH HHS R01 GM140078NIGMS NIH HHS R35 GM159978
6 · The paper itself

Abstract

Biased signaling by G protein-coupled receptors (GPCRs) occurs when ligands selectively activate G proteins or β-arrestins, offering therapeutic potential with fewer side effects. In class A GPCRs, which include the targets of approximately one-third of all marketed drugs, the structural basis of this selectivity remains unclear. Recent cryo-electron microscopy studies, supported by real-time functional assays such as bioluminescence resonance energy transfer and NanoLuc Binary Technology, reveal how distinct ligand binding modes reshape receptor conformations to favor specific transducer engagement. Integrating structural and functional insights enables mapping of isoform- and tissue-specific signaling. Here, we review key mechanisms of bias, including microswitch transitions, intracellular interface remodeling, and allosteric modulation, and provide a mechanistic basis for pathway-selective GPCR-targeting therapeutics with improved efficacy and reduced off-target effects.

Indexed as

Receptors, G-Protein-CoupledSignal TransductionAnimalsHumansLigandsLigandsReceptors, G-Protein-Coupledbiased signalingbioluminescence resonance energy transfer (BRET)cryo–electron microscopy (cryo-EM)G protein–coupled receptors (GPCRs)NanoLuc Binary Technology (NanoBiT)structure-based drug design (SBDD)

Identifiers

PMID41206221
PMCPMC12991348

What Socratic holds

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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.