ArticleProceedings of the National Academy of Sciences of the United States of America2015
CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled 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.
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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Effect of recreational cannabis use on bone mineral density: a systematic review.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024Pooled it
- Synthesis of Novel Chloro-Benzo [Pharmaceuticals (Basel, Switzerland) · 2025Article
- Review
- Enantiomeric Agonists of the Type 2 Cannabinoid Receptor Reduce Retinal Damage during Proliferative Vitreoretinopathy and Inhibit Hyperactive MicrogliaACS pharmacology & translational science · 2024Article
- CB2 regulates oxidative stress and osteoclastogenesis through NOX1-dependent signaling pathway in titanium particle-induced osteolysis.Cell death discovery · 2023Article
- Development of a membrane-based Gi-CASE biosensor assay for profiling compounds at cannabinoid receptors.Frontiers in pharmacology · 2023Article
- Article
- Fenchone Derivatives as a Novel Class of CB2 Selective Ligands: Design, Synthesis, X-ray Structure and Therapeutic Potential.Molecules (Basel, Switzerland) · 2022Article
- The Role of Cannabinoids in Bone Metabolism: A New Perspective for Bone Disorders.International journal of molecular sciences · 2021Review
- Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models.Molecules (Basel, Switzerland) · 2021Review
- Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders.Molecules (Basel, Switzerland) · 2021Review
- Components of the Endocannabinoid System and Effects of Cannabinoids Against Bone Diseases: A Mini-Review.Frontiers in pharmacology · 2021Review
- The Cannabinoids Effect on Bone Formation and Bone Healing.Current osteoporosis reports · 2020Review
- A Guide to Targeting the Endocannabinoid System in Drug Design.International journal of molecular sciences · 2020Review
- Endocannabinoid Modulation of Microglial Phenotypes in Neuropathology.Frontiers in neurology · 2020Review
- Antioxidative and Anti-Inflammatory Properties of Cannabidiol.Antioxidants (Basel, Switzerland) · 2019Review
- Roles of the Hepatic Endocannabinoid and Apelin Systems in the Pathogenesis of Liver Fibrosis.Cells · 2019Review
- HU-671, a Novel Oleoyl Serine Derivative, Exhibits Enhanced Efficacy in Reversing Ovariectomy-Induced Osteoporosis and Bone Marrow Adiposity.Molecules (Basel, Switzerland) · 2019Article
- Receptor Binding Affinities of Synthetic Cannabinoids Determined by Non-Isotopic Receptor Binding Assay.Toxicological research · 2019Article
- The exogenous administration of CB2 specific agonist, GW405833, inhibits inflammation by reducing cytokine production and oxidative stress.Experimental and therapeutic medicine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Activation of the CB2 receptor is apparently an endogenous protective mechanism. Thus, it restrains inflammation and protects the skeleton against age-related bone loss. However, the endogenous cannabinoids, as well as Δ(9)-tetrahydrocannabinol, the main plant psychoactive constituent, activate both cannabinoid receptors, CB1 and CB2. HU-308 was among the first synthetic, selective CB2 agonists. HU-308 is antiosteoporotic and antiinflammatory. Here we show that the HU-308 enantiomer, designated HU-433, is 3-4 orders of magnitude more potent in osteoblast proliferation and osteoclast differentiation culture systems, as well as in mouse models, for the rescue of ovariectomy-induced bone loss and ear inflammation. HU-433 retains the HU-308 specificity for CB2, as shown by its failure to bind to the CB1 cannabinoid receptor, and has no activity in CB2-deficient cells and animals. Surprisingly, the CB2 binding affinity of HU-433 in terms of [(3)H]CP55,940 displacement and its effect on [(35)S]GTPγS accumulation is substantially lower compared with HU-308. A molecular-modeling analysis suggests that HU-433 and -308 have two different binding conformations within CB2, with one of them possibly responsible for the affinity difference, involving [(35)S]GTPγS and cAMP synthesis. Hence, different ligands may have different orientations relative to the same binding site. This situation questions the usefulness of universal radioligands for comparative binding studies. Moreover, orientation-targeted ligands have promising potential for the pharmacological activation of distinct processes.
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.