ArticleThe Journal of biological chemistry2012
A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed.
- UDP-glucose and MRS2905 agonist-bound states of the purinergic P2YCommunications biology · 2025Article
- Discovery, Characterization, and Optimization of a Novel Positive Allosteric Modulator-Antagonist of the DJournal of medicinal chemistry · 2025Article
- Development of Squaramides as Allosteric Modulators of the CBJournal of medicinal chemistry · 2025Article
- Insight into the mechanism of action of ORG27569 at the cannabinoid type one receptor utilising a unified mathematical model.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- A rapid, tag-free way to purify functional GPCRs.The Journal of biological chemistry · 2024Article
- The NPXXY Motif Regulates β-Arrestin Recruitment by the CB1 Cannabinoid Receptor.Cannabis and cannabinoid research · 2023Article
- Discovery and Characterization of the First Nonpeptide Antagonists for the Relaxin-3/RXFP3 System.Journal of medicinal chemistry · 2022Article
- Structure of an allosteric modulator bound to the CB1 cannabinoid receptor.Nature chemical biology · 2019Article
- Indomethacin Enhances Type 1 Cannabinoid Receptor Signaling.Frontiers in molecular neuroscience · 2019Article
- Single Proteoliposome High-Content Analysis Reveals Differences in the Homo-Oligomerization of GPCRs.Biophysical journal · 2018Article
- Modulation of CB1 cannabinoid receptor by allosteric ligands: Pharmacology and therapeutic opportunities.Neuropharmacology · 2017Review
- Assessing Allosteric Modulation of CBMethods in enzymology · 2017Article
- Leveraging allostery to improve G protein-coupled receptor (GPCR)-directed therapeutics: cannabinoid receptor 1 as discovery target.Expert opinion on drug discovery · 2016Review
- Decay of an active GPCR: Conformational dynamics govern agonist rebinding and persistence of an active, yet empty, receptor state.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Synthesis and biological evaluation of indole-2-carboxamides bearing photoactivatable functionalities as novel allosteric modulators for the cannabinoid CB1 receptor.European journal of medicinal chemistry · 2016Article
- Mapping Cannabinoid 1 Receptor Allosteric Site(s): Critical Molecular Determinant and Signaling Profile of GAT100, a Novel, Potent, and Irreversibly Binding Probe.ACS chemical neuroscience · 2016Article
- Zinc Is Involved in Depression by Modulating G Protein-Coupled Receptor Heterodimerization.Molecular neurobiology · 2016Article
- Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s).Journal of medicinal chemistry · 2016Article
- In-Membrane Chemical Modification (IMCM) for Site-Specific Chromophore Labeling of GPCRs.Angewandte Chemie (International ed. in English) · 2015Article
- Structural dynamics and energetics underlying allosteric inactivation of the cannabinoid receptor CB1.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Allosteric ligands that modulate how G protein-coupled receptors respond to traditional orthosteric drugs are an exciting and rapidly expanding field of pharmacology. An allosteric ligand for the cannabinoid receptor CB1, Org 27569, exhibits an intriguing effect; it increases agonist binding, yet blocks agonist-induced CB1 signaling. Here we explored the mechanism behind this behavior, using a site-directed fluorescence labeling approach. Our results show that Org 27569 blocks conformational changes in CB1 that accompany G protein binding and/or activation, and thus inhibit formation of a fully active CB1 structure. The underlying mechanism behind this behavior is that simultaneous binding of Org 27569 produces a unique agonist-bound conformation, one that may resemble an intermediate structure formed on the pathway to full receptor activation.
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.