ReviewThe Journal of biological chemistry2025
Constitutively active orphan G protein-coupled receptors through the lenses of cryo-electron microscopy.
Review in The Journal of biological chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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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.
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Who cites it
2 citing papers in PubMed.
- Shining a light on orphan GPCRs.Nature chemical biology · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein-coupled receptors (GPCRs) are a therapeutically privileged family of receptors involved in a wide variety of pathophysiological conditions and the successful target for ∼34% of FDA-approved drugs. However, a significant percentage of GPCRs remain orphan, i.e., the endogenous ligands that modulate receptor function are unknown, and hence knowledge about their functional role and the generation of new therapeutics lag behind. During recent years, the use of cryo-electron microscopy has revolutionized GPCR structural biology including its application to orphan GPCRs, especially those displaying constitutive activity in cellular model systems. Such efforts have resulted in the description of new modes of in-built agonists that include the ECL2 and N-terminal regions as well as identifying ubiquitous endogenous ligands readily bound to GPCRs. These results position structural determination as a new key component in GPCR deorphanization, shedding light on new signaling mechanisms, bringing questions about their functional regulation, and opening new avenues for drug design.
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