ArticleNeurochemical research2014
mGluR5: exploration of orthosteric and allosteric ligand binding pockets and their applications to drug discovery.
Article in Neurochemical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window.The international journal of neuropsychopharmacology · 2016Pooled it
- Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.ACS pharmacology & translational science · 2024Review
- 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
- Reduced Metabotropic Glutamate Receptor Type 5 Availability in the Epileptogenic Hippocampus: AnFrontiers in neurology · 2022Article
- Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?Frontiers in pharmacology · 2022Review
- Agonists and allosteric modulators promote signaling from different metabotropic glutamate receptor 5 conformations.Cell reports · 2021Article
- Allosteric Molecular Switches in Metabotropic Glutamate Receptors.ChemMedChem · 2021Review
- Profiling the Structural Determinants of Aryl Benzamide Derivatives as Negative Allosteric Modulators of mGluR5 by In Silico Study.Molecules (Basel, Switzerland) · 2020Article
- The role of water and protein flexibility in the structure-based virtual screening of allosteric GPCR modulators: an mGluJournal of computer-aided molecular design · 2019Article
- Advantages of Structure-Based Drug Design Approaches in Neurological Disorders.Current neuropharmacology · 2017Review
- Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer's Mouse Phenotypes.Cell reports · 2017Article
- Selective Negative Allosteric Modulation Of Metabotropic Glutamate Receptors – A Structural Perspective of Ligands and Mutants.Scientific reports · 2015Article
- Virtual Screening and Molecular Dynamics Study of Potential Negative Allosteric Modulators of mGluR1 from Chinese Herbs.Molecules (Basel, Switzerland) · 2015Article
- Allosteric Binding Site and Activation Mechanism of Class C G-Protein Coupled Receptors: Metabotropic Glutamate Receptor Family.The AAPS journal · 2015Article
- Generic GPCR residue numbers - aligning topology maps while minding the gaps.Trends in pharmacological sciences · 2015Review
- Therapeutic molecules and endogenous ligands regulate the interaction between brain cellular prion protein (PrPC) and metabotropic glutamate receptor 5 (mGluR5).The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since its discovery in 1992, mGluR5 has attracted significant attention and been linked to several neurological and psychiatric diseases. Ligand development was initially focused on the orthosteric binding pocket, but lack of subtype selective ligands changed the focus to the transmembrane allosteric binding pocket. This strategy has resulted in several drug candidates in clinical testing. In the present article we explore the orthosteric and allosteric binding pockets in terms of structure and ligand recognition across the mGluR subtypes and groups, and discuss the clinical potential of ligands targeting these pockets. We have performed binding mode analyses of non- and group-selective orthosteric ligands based on molecular docking in mGluR crystal structures and models. For the analysis of the allosteric binding pocket we have combined data from all mGluR5-mutagenesis studies, collectively reporting five negative allosteric modulators and 47 unique mutations, and compared it to the closest related homolog, mGluR1.
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Identifiers
24493625What 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.