ArticleBiochemistry2013
Identification of the GPR55 antagonist binding site using a novel set of high-potency GPR55 selective ligands.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 99 citations in OpenAlex.
- Activating GPR55 protects cochlear hair cells against cisplatin-induced ototoxicity via inhibiting MAPK pathway.Scientific reports · 2026Article
- Pharmacological advances in cannabinoid-based therapies for pancreatic cancer: preclinical efficacy of CCL-106 and its epimers.ESMO gastrointestinal oncology · 2025Article
- Unraveling the Mechanisms of Cannabidiol's Pharmacological Actions: A Comprehensive Research Overview.Topics in current chemistry (Cham) · 2024Review
- Article
- Exploring orphan GPCRs in neurodegenerative diseases.Frontiers in pharmacology · 2024Review
- The TRPV1 Receptor Is Up-Regulated by Sphingosine 1-Phosphate and Is Implicated in the Anandamide-Dependent Regulation of Mitochondrial Activity in C2C12 Myoblasts.International journal of molecular sciences · 2022Article
- Interacting binding insights and conformational consequences of the differential activity of cannabidiol with two endocannabinoid-activated G-protein-coupled receptors.Frontiers in pharmacology · 2022Article
- Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators.Frontiers in molecular biosciences · 2022Article
- GPR55-mediated effects on brain microvascular endothelial cells and the blood-brain barrier.Neuroscience · 2019Article
- Discovery of 1,4-Naphthoquinones as a New Class of Antiproliferative Agents Targeting GPR55.ACS medicinal chemistry letters · 2019Article
- Discovery and Optimization of Selective and in Vivo Active Inhibitors of the Lysophosphatidylserine Lipase α/β-Hydrolase Domain-Containing 12 (ABHD12).Journal of medicinal chemistry · 2019Article
- New Insights in Cannabinoid Receptor Structure and Signaling.Current molecular pharmacology · 2019Review
- GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- The Spastic Paraplegia-Associated Phospholipase DDHD1 Is a Primary Brain Phosphatidylinositol Lipase.Biochemistry · 2018Article
- Understanding the endocannabinoid system as a modulator of the trigeminal pain response to concussion.Concussion (London, England) · 2017Review
- Design, synthesis and biological evaluation of GPR55 agonists.Bioorganic & medicinal chemistry · 2017Article
- The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress.Molecular brain · 2017Article
- Identification of Crucial Amino Acid Residues Involved in Agonist Signaling at the GPR55 Receptor.Biochemistry · 2017Article
- Advances in the Physiology of GPR55 in the Central Nervous System.Current neuropharmacology · 2017Review
- Design, synthesis, and analysis of antagonists of GPR55: Piperidine-substituted 1,3,4-oxadiazol-2-ones.Bioorganic & medicinal chemistry letters · 2016Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
GPR55 is a class A G protein-coupled receptor (GPCR) that has been implicated in inflammatory pain, neuropathic pain, metabolic disorder, bone development, and cancer. Initially deorphanized as a cannabinoid receptor, GPR55 has been shown to be activated by non-cannabinoid ligands such as l-α-lysophosphatidylinositol (LPI). While there is a growing body of evidence of physiological and pathophysiological roles for GPR55, the paucity of specific antagonists has limited its study. In collaboration with the Molecular Libraries Probe Production Centers Network initiative, we identified a series of GPR55 antagonists using a β-arrestin, high-throughput, high-content screen of ~300000 compounds. This screen yielded novel, GPR55 antagonist chemotypes with IC50 values in the range of 0.16-2.72 μM [Heynen-Genel, S., et al. (2010) Screening for Selective Ligands for GPR55: Antagonists (ML191, ML192, ML193) (Bookshelf ID NBK66153; PMID entry 22091481)]. Importantly, many of the GPR55 antagonists were completely selective, with no agonism or antagonism against GPR35, CB1, or CB2 up to 20 μM. Using a model of the GPR55 inactive state, we studied the binding of an antagonist series that emerged from this screen. These studies suggest that GPR55 antagonists possess a head region that occupies a horizontal binding pocket extending into the extracellular loop region, a central ligand portion that fits vertically in the receptor binding pocket and terminates with a pendant aromatic or heterocyclic ring that juts out. Both the region that extends extracellularly and the pendant ring are features associated with antagonism. Taken together, our results provide a set of design rules for the development of second-generation GPR55 selective antagonists.
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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.