ReviewBiochemistry2011
"Molecular switches" on mGluR allosteric ligands that modulate modes of pharmacology.
Review in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 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
80 citing papers in PubMed.
- mGlu4R, mGlu7R, and mGlu8R allosteric modulation for treating acute and chronic neurodegenerative disorders.Pharmacological reports : PR · 2024Review
- The novel peptide LCGM-10 attenuates metabotropic glutamate receptor 5 activity and demonstrates behavioral effects in animal models.Frontiers in behavioral neuroscience · 2024Article
- Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks.Pharmaceuticals (Basel, Switzerland) · 2023Review
- PET imaging studies to investigate functional expression of mGluR2 using [Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Structure-Based Discovery of Negative Allosteric Modulators of the Metabotropic Glutamate Receptor 5.ACS chemical biology · 2022Article
- Discovery of "Molecular Switches" within a Series of mGluACS bio & med chem Au · 2021Article
- The Deuterated "Magic Methyl" Group: A Guide to Site-Selective Trideuteromethyl Incorporation and Labeling by Using CDChemistry (Weinheim an der Bergstrasse, Germany) · 2021Review
- Study of influence of the glutamatergic concentration of [Translational psychiatry · 2021Article
- Allosteric Molecular Switches in Metabotropic Glutamate Receptors.ChemMedChem · 2021Review
- Mechanistic Insights into Light-Driven Allosteric Control of GPCR Biological Activity.ACS pharmacology & translational science · 2020Article
- Exploring the Activation Mechanism of the mGlu5 Transmembrane Domain.Frontiers in molecular biosciences · 2020Article
- Design, Synthesis, and Characterization of Ogerin-Based Positive Allosteric Modulators for G Protein-Coupled Receptor 68 (GPR68).Journal of medicinal chemistry · 2019Article
- Evaluation of Synthetic Cytochrome PACS omega · 2019Article
- Discovery of Tricyclic Triazolo- and Imidazopyridine Lactams as MACS chemical neuroscience · 2019Article
- Palladium-Catalyzed Methylation of Aryl, Heteroaryl, and Vinyl Boronate Esters.Organic letters · 2019Article
- Allosteric Modulation of Class A GPCRs: Targets, Agents, and Emerging Concepts.Journal of medicinal chemistry · 2019Review
- The neurotoxicity induced by PMToxicology research · 2018Article
- Isoxazolo[3,4-d]pyridazinones positively modulate the metabotropic glutamate subtypes 2 and 4.Bioorganic & medicinal chemistry · 2018Article
- Structure-Activity Relationships of Pan-GαACS chemical neuroscience · 2018Article
- Group II Metabotropic Glutamate Receptors: Role in Pain Mechanisms and Pain Modulation.Frontiers in molecular neuroscience · 2018Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
G-protein-coupled receptors (GPCRs) represent the largest class of drug targets, accounting for more than 40% of marketed drugs; however, discovery efforts for many GPCRs have failed to provide viable drug candidates. Historically, drug discovery efforts have focused on developing ligands that act at the orthosteric site of the endogenous agonist. Recently, efforts have focused on functional assay paradigms and the discovery of ligands that act at allosteric sites to modulate receptor function in either a positive, negative, or neutral manner. Allosteric modulators have numerous advantages over orthosteric ligands, including high subtype selectivity; the ability to mimic physiological conditions; the lack of densensitization, downregulation, and internalization; and reduced side effects. Despite these virtues, challenging issues have now arisen for allosteric modulators of metabotropic glutamate receptors (mGluRs): shallow SAR, ligand-directed trafficking, and the identification of subtle "molecular switches" that modulate the modes of pharmacology. Here, we will discuss the impact of modest structural changes to multiple mGluR allosteric ligands scaffolds that unexpectedly modulate pharmacology and raise concerns over metabolism and the pharmacology of metabolites.
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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.