ArticleNature chemical biology2019
Structure of an allosteric modulator bound to the CB1 cannabinoid receptor.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 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
105 citing papers in PubMed, 174 citations in OpenAlex.
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- Article
- Side-Chain Homologs of ΔMolecular neurobiology · 2026Article
- Library Docking for Cannabinoid-2 Receptor Ligands.Journal of medicinal chemistry · 2026Article
- Dynamic mechanism for subtype selectivity of endocannabinoids.The Journal of biological chemistry · 2026Article
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the µ-opioid receptor.Nature communications · 2026Article
- Overlapping pathways of migraine and the endocannabinoid system: Potential therapeutic targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Cannabidiphorol (CBDP) acts as a negative allosteric modulator at two distinct sites of cannabinoid receptor 1.Communications chemistry · 2026Article
- Library docking for Cannabinoid-2 Receptor ligands.bioRxiv : the preprint server for biology · 2026Article
- Structural Perspectives on Biased Allostery of GPCR Signaling.Handbook of experimental pharmacology · 2026Review
- Cannabinoid-based Pharmacology for the Management of Substance Use Disorders.Current topics in behavioral neurosciences · 2026Review
- Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026Review
- Decoding ligand recognition and constitutive activation of histamine H3 and H4 receptors.Acta pharmacologica Sinica · 2026Article
- Allosteric Modulation of Cannabinoid Type 1 Receptor by ZCZ011: Integration of In Vitro Pharmacology and Molecular Dynamics Simulation.ACS bio & med chem Au · 2025Article
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- G Protein-Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers.MedComm · 2025Review
- Synthesis of New N,N'-Diarylureas and Their Theoretical Study as Cannabinoid-1 Receptor Inhibitors.ChemPlusChem · 2025Article
- Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery.Acta pharmacologica Sinica · 2025Review
- Cryo-EM reveals cholesterol binding in the lysosomal GPCR-like protein LYCHOS.Nature structural & molecular biology · 2025Article
45 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
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CB1 receptor mediates the central nervous system response to cannabinoids, and is a drug target for pain, anxiety and seizures. CB1 also responds to allosteric modulators, which influence cannabinoid binding and efficacy. To understand the mechanism of these compounds, we solved the crystal structure of CB1 with the negative allosteric modulator (NAM) ORG27569 and the agonist CP55940. The structure reveals that the NAM binds to an extrahelical site within the inner leaflet of the membrane, which overlaps with a conserved site of cholesterol interaction in many G protein-coupled receptors (GPCRs). The ternary structure with ORG27569 and CP55940 captures an intermediate state of the receptor, in which aromatic residues at the base of the agonist-binding pocket adopt an inactive conformation despite the large contraction of the orthosteric pocket. The structure illustrates a potential strategy for drug modulation of CB1 and other class A GPCRs.
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.