Cargando…

Challenges in the Discovery and Optimization of mGlu(2/4) Heterodimer Positive Allosteric Modulators

BACKGROUND: This article describes the challenges in the discovery and optimization of mGlu2/4 heterodimer Positive Allosteric Modulators (PAMs). METHODS: Initial forays based on VU0155041, a PAM of both the mGlu4 homodimer and the mGlu2/4 heterodimer, led to flat, intractable SAR that precluded adv...

Descripción completa

Detalles Bibliográficos
Autores principales:	Fulton, Mark Gallant, Loch, Matthew Thomas, Cuoco, Caroline Anne, Rodriguez, Alice Lambert, Days, Emily, Vinson, Paige Newton, Kozek, Krystian Andrezej, Weaver, Charles David, Blobaum, Anna Louise, Conn, Peter Jeffrey, Niswender, Colleen Marie, Lindsley, Craig William
Formato:	Online Artículo Texto
Lenguaje:	English
Publicado:	Bentham Science Publishers 2019
Materias:	Letters in Drug Design & Discovery
Acceso en línea:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059629/ https://www.ncbi.nlm.nih.gov/pubmed/32201485 http://dx.doi.org/10.2174/1570180815666181017131349

Ejemplares similares

Differential activity of mGlu(7) allosteric modulators provides evidence for mGlu(7/8) heterodimers at hippocampal Schaffer collateral-CA1 synapses
por: Lin, Xin, et al.
Publicado: (2022)

mGlu(5) Positive Allosteric Modulators Facilitate Long-Term Potentiation via Disinhibition Mediated by mGlu(5)-Endocannabinoid Signaling
por: Xiang, Zixiu, et al.
Publicado: (2019)

Discovery of a Novel Chemical Class of mGlu(5) Allosteric Ligands with Distinct Modes of Pharmacology
por: Hammond, Alexis S., et al.
Publicado: (2010)

Structural insights into dimerization and activation of the mGlu2–mGlu3 and mGlu2–mGlu4 heterodimers
por: Wang, Xinwei, et al.
Publicado: (2023)

Neurobiological Insights from mGlu Receptor Allosteric Modulation
por: O’Brien, Daniel E, et al.
Publicado: (2015)

Tetrahydronaphthyridine and Dihydronaphthyridinone Ethers As Positive Allosteric Modulators of the Metabotropic Glutamate Receptor 5 (mGlu(5))
por: Turlington, Mark, et al.
Publicado: (2014)

Evaluation of Synthetic Cytochrome P(450)-Mimetic Metalloporphyrins To Facilitate “Biomimetic” Biotransformation of a Series of mGlu(5) Allosteric Ligands
por: Presley, Christopher C., et al.
Publicado: (2019)

Allosteric Modulators for mGlu Receptors
por: Gasparini, F, et al.
Publicado: (2007)

The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies
por: Senter, Rebecca K., et al.
Publicado: (2016)

Extracting Atomic Contributions to Binding Free Energy using Molecular Dynamics Simulations with Mixed Solvents (MDmix)
por: Alvarez-Garcia, Daniel, et al.
Publicado: (2022)

Event Monitoring and Evaluation by Community Pharmacists in Japan: A Pilot Study on Fenofibrate and Pemafibrate
por: Takahashi, Masao, et al.
Publicado: (2022)

Key Targets and Molecular Mechanisms of Active Volatile Components of Rabdosia rubescens in Gastric Cancer Cells
por: Hu, Yanhui, et al.
Publicado: (2022)

Lack of Evidence for Blood Pressure Effects of Caffeine Added to Ibuprofen
por: Lampert, Anette, et al.
Publicado: (2023)

Analysis of Intoxication, Rehospitalization, and One-year Survival of Heart Failure Patients Receiving Digoxin at Harapan Kita National Cardiovascular Center, Jakarta, Indonesia: A Cross Section-observational Study
por: Nafrialdi, Nafrialdi, et al.
Publicado: (2023)

Drug-induced Sudden Death: A Scoping Review
por: Amaro-Hosey, Kristopher, et al.
Publicado: (2023)

Multidrug Resistance-1 C3435T Polymorphism and Carbamazepine Plasma Level in Indonesian Temporal Lobe Epilepsy Patients
por: Budikayanti, Astri, et al.
Publicado: (2023)

Remimazolam and Remifentanil Use Induced Severe Respiratory Depression and Laryngeal Spasm During Intravenous Sedation and Analgesia: A Case Report
por: Xin, Zhijun, et al.
Publicado: (2023)

Osimertinib-induced Keratitis and Secondary Toxic Epidermal Necrotic Drug Eruption- A Case Report and Literature Review
por: Xu, Yunhua, et al.
Publicado: (2023)

mGlu(1) potentiation enhances prelimbic somatostatin interneuron activity to rescue schizophrenia-like physiological and cognitive deficits
por: Maksymetz, James, et al.
Publicado: (2021)

Pharmacokinetics and Tissue Distribution of Nasal Spray of a Novel Muscarinic Receptor Blocker, 101BHG-D01, in Dogs and Rats
por: Wei, Hao, et al.
Publicado: (2022)

Regulation and functional consequences of mGlu(4) RNA editing
por: Hofmann, Christopher S., et al.
Publicado: (2021)

Discovery of “Molecular Switches” within a Series of mGlu(5) Allosteric Ligands Driven by a “Magic Methyl” Effect Affording Both PAMs and NAMs with In Vivo Activity, Derived from an M(1) PAM Chemotype
por: Barbaro, Lisa, et al.
Publicado: (2021)

Negative Allosteric Modulators of mGlu(7) Receptor as Putative Antipsychotic Drugs
por: Cieślik, Paulina, et al.
Publicado: (2018)

Chemical Modulation of Mutant mGlu(1) Receptors Derived from Deleterious GRM1 Mutations Found in Schizophrenics
por: Cho, Hyekyung P., et al.
Publicado: (2014)

A GRM7 mutation associated with developmental delay reduces mGlu(7) expression and produces neurological phenotypes
por: Fisher, Nicole M., et al.
Publicado: (2021)

Preclinical evaluation of the antipsychotic potential of the mGlu2-positive allosteric modulator JNJ-40411813
por: Lavreysen, Hilde, et al.
Publicado: (2015)

mGlu2 metabotropic glutamate receptors restrain inflammatory pain and mediate the analgesic activity of dual mGlu2/mGlu3 receptor agonists
por: Zammataro, Magda, et al.
Publicado: (2011)

Pharmacological and pharmacokinetic properties of JNJ-40411813, a positive allosteric modulator of the mGlu2 receptor
por: Lavreysen, Hilde, et al.
Publicado: (2015)

Optical control of pain in vivo with a photoactive mGlu(5) receptor negative allosteric modulator
por: Font, Joan, et al.
Publicado: (2017)

Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation
por: Scholler, Pauline, et al.
Publicado: (2017)

Correction: Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator
por: Font, Joan, et al.
Publicado: (2018)

43.1 GENETIC INSIGHTS LEAD TO DISCOVERY OF SELECTIVE ACTIVATORS OF MGLU1 AND MGLU3 METABOTROPIC GLUTAMATE RECEPTORS AS POTENTIAL TREATMENTS FOR SCHIZOPHRENIA
por: Conn, P Jeffrey, et al.
Publicado: (2018)

Partial mGlu(5) Negative Allosteric Modulator M-5MPEP Demonstrates Antidepressant-Like Effects on Sleep Without Affecting Cognition or Quantitative EEG
por: Holter, Kimberly M., et al.
Publicado: (2021)

Drugs in the GIST Field (Therapeutic Targets and Clinical Trial Staging)
por: Huang, Chen, et al.
Publicado: (2023)

Decreased striatal dopamine in group II metabotropic glutamate receptor (mGlu2/mGlu3) double knockout mice
por: Lane, Tracy A, et al.
Publicado: (2013)

Emotional Impairment and Persistent Upregulation of mGlu(5) Receptor following Morphine Abstinence: Implications of an mGlu(5)-MOPr Interaction
por: Zanos, Panos, et al.
Publicado: (2016)

mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors
por: Notartomaso, Serena, et al.
Publicado: (2018)

Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain
por: Moloney, Rachel D., et al.
Publicado: (2015)

mGlu5 Receptor Functional Interactions and Addiction
por: Brown, Robyn M., et al.
Publicado: (2012)

In vivo Metabolism of Nifurtimox and the Drug-Drug Interaction Potential Including its Major Metabolites
por: Schulz, Simone I., et al.
Publicado: (2023)

Cannot write session to /tmp/vufind_sessions/sess_ns6jbkelhokk08r8f4akjosqsk