ArticleMolecular pharmacology2016
Discovery and Characterization of Novel GPR39 Agonists Allosterically Modulated by Zinc.
Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 58 citations in OpenAlex.
- Novel Roles of GPCRs in the Renal Collecting Duct.Physiology (Bethesda, Md.) · 2026Review
- Zinc Signaling in Acute Kidney Injury.Cells · 2026Review
- GPR39 activation inhibits AQP2 trafficking and alters cytoskeletal organization.American journal of physiology. Cell physiology · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- GPCRs as key regulators in wound healing.Frontiers in cell and developmental biology · 2026Review
- Investigating the role of GPR39 in treatment of stress-induced depression and anxiety.Psychopharmacology · 2025Article
- Illuminating the druggable genome: Pathways to progress.Drug discovery today · 2024Review
- GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.Science advances · 2024Article
- Making Sense of Psychedelics in the CNS.The international journal of neuropsychopharmacology · 2024Article
- Unlocking the brain's zinc code: implications for cognitive function and disease.Frontiers in biophysics · 2024Article
- The role of GPR39 zinc receptor in the modulation of glutamatergic and GABAergic transmission.Pharmacological reports : PR · 2023Article
- Signaling pathway mechanisms of neurological diseases induced by G protein-coupled receptor 39.CNS neuroscience & therapeutics · 2023Review
- TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice.Cellular and molecular life sciences : CMLS · 2023Article
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
- Article
- The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms.Prostaglandins & other lipid mediators · 2022Article
- Article
- Control of coronary vascular resistance by eicosanoids via a novel GPCR.American journal of physiology. Cell physiology · 2022Article
- Role of GPR39 in Neurovascular Homeostasis and Disease.International journal of molecular sciences · 2021Review
- The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In this study, we identified two previously described kinase inhibitors-3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(3-methyl-1H-pyrazol-5-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine (LY2784544) and 1H-benzimidazole-4-carboxylic acid, 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-(4-morpholinyl)- (GSK2636771)-as novel GPR39 agonists by unbiased small-molecule-based screening using a β-arrestin recruitment screening approach (PRESTO-Tango). We characterized the signaling of LY2784544 and GSK2636771 and compared their signaling patterns with a previously described "GPR39-selective" agonist N-[3-chloro-4-[[[2-(methylamino)-6-(2-pyridinyl)-4- pyrimidinyl]amino]methyl]phenyl]methanesulfonamide (GPR39-C3) at both canonical and noncanonical signaling pathways. Unexpectedly, all three compounds displayed probe-dependent and pathway-dependent allosteric modulation by concentrations of zinc reported to be physiologic. LY2784544 and GS2636771 at GPR39 in the presence of zinc were generally as potent or more potent than their reported activities against kinases in whole-cell assays. These findings reveal an unexpected role of zinc as an allosteric potentiator of small-molecule-induced activation of GPR39 and expand the list of potential kinase off-targets to include understudied G protein-coupled receptors.
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.