Evidence map›Paper›PMID 30639103›Full record

ArticleCell2019

Crystal Structure of the Human Cannabinoid Receptor CB2.

Xiaoting Li, Tian Hua, Kiran Vemuri, Jo-Hao Ho, Yiran Wu, Lijie Wu, Petr Popov, Othman Benchama, Nikolai Zvonok, K'ara Locke and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
186citing papers in PubMed, 1 pooled it
–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

186 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Library Docking for Cannabinoid-2 Receptor Ligands.Journal of medicinal chemistry · 2026
    Article
  5. Article
  6. Dynamic mechanism for subtype selectivity of endocannabinoids.The Journal of biological chemistry · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Targeting the LPI/GPR55 Axis in MAFLD and MASH: Novel Insights, Therapeutic Strategies and Future Directions.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Review
  12. Article
  13. Library docking for Cannabinoid-2 Receptor ligands.bioRxiv : the preprint server for biology · 2026
    Article
  14. Article
  15. Genetically Encoded CBInternational journal of molecular sciences · 2026
    Article
  16. Article
  17. Article
  18. Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026
    Review
  19. Review
  20. Article

126 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Xiaoting LiiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
Tian HuaiHuman Institute, ShanghaiTech University, Shanghai 201210, China.
Kiran VemuriCenter for Drug Discovery, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Jo-Hao HoDepartment of Molecular Medicine, Scripps Research, Jupiter, FL 33458, USA.
Yiran WuiHuman Institute, ShanghaiTech University, Shanghai 201210, China.
Lijie WuiHuman Institute, ShanghaiTech University, Shanghai 201210, China.
Petr PopovDepartment of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA; Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
Othman BenchamaCenter for Drug Discovery, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Nikolai ZvonokCenter for Drug Discovery, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
K'ara LockeDepartment of Molecular Medicine, Scripps Research, Jupiter, FL 33458, USA.
Lu QuiHuman Institute, ShanghaiTech University, Shanghai 201210, China.
Gye Won HanDepartment of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA.
Malliga R IyerLaboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
Resat CinarLaboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
Nathan J CoffeyLaboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
Jingjing WangiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
Meng WuiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
Vsevolod KatritchDepartment of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA; Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
Suwen ZhaoiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
George KunosLaboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
Laura M BohnDepartment of Molecular Medicine, Scripps Research, Jupiter, FL 33458, USA.
Alexandros MakriyannisCenter for Drug Discovery, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Raymond C StevensiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Department of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA.
Zhi-Jie LiuiHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address: liuzhj@shanghaitech.edu.cn.

Funding

Endocannabinoids And Energy HomeostasisZIAAA000350 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI KUNOS, GEORGE · 2009 to 2025
$28.4M
Project 3 - In vivo pharmacology of cannabinoid receptor probesP01DA009158 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI Alexandros Makriyannis · 1994 to 2026
$26.0M
Structure and Function of CB2 ReceptorR01DA045020 · NIDA · NORTHEASTERN UNIVERSITY · PI BOHN, LAURA M., KATRITCH, VSEVOLOD · 2017 to 2021
$3.9M
Structure Function of CB1 Cannabinoid ReceptorR01DA041435 · NIDA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KATRITCH, VSEVOLOD, MAKRIYANNIS, ALEXANDROS · 2016 to 2020
$3.6M
NIDA NIH HHS P01 DA009158NIDA NIH HHS R01 DA041435NIDA NIH HHS R01 DA045020
6 · The paper itself

Abstract

The cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of CB2 without the psychoactivity of CB1 has therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases. Here, we report the crystal structure of human CB2 in complex with a rationally designed antagonist, AM10257, at 2.8 Å resolution. The CB2-AM10257 structure reveals a distinctly different binding pose compared with CB1. However, the extracellular portion of the antagonist-bound CB2 shares a high degree of conformational similarity with the agonist-bound CB1, which led to the discovery of AM10257's unexpected opposing functional profile of CB2 antagonism versus CB1 agonism. Further structural analysis using mutagenesis studies and molecular docking revealed the molecular basis of their function and selectivity for CB2 and CB1. Additional analyses of our designed antagonist and agonist pairs provide important insight into the activation mechanism of CB2. The present findings should facilitate rational drug design toward precise modulation of the endocannabinoid system.

Indexed as

AnimalsCannabinoid Receptor AntagonistsCannabinoidsDrug DesignEndocannabinoidsHumansLigandsMolecular Docking SimulationProtein BindingReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Receptors, CannabinoidReceptors, G-Protein-CoupledSf9 CellsStructure-Activity RelationshipCannabinoid Receptor AntagonistsCannabinoidsEndocannabinoidsLigandsReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Receptors, CannabinoidReceptors, G-Protein-Coupledcannabinoid receptor CB2crystal structureG-protein coupled receptorligand designsubtype selectivity

Identifiers

PMID30639103
PMCPMC6713262

What OpenQuestion holds

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Registered trials

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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.