Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
This letter describes synthesis and evaluation of two series of dual mGlu/mGlu positive allosteric modulators with moderate mGlu potency and robust mGlu potency in thallium flux assays. These compounds were profiled their ability to modulate mGlu-mediated signaling in central neurons by co-application of a selective mGlu NAM to isolate mGlu-selective effects. Using acute mouse brain slices from the prefrontal cortex, potentiation of group II mGlu receptor agonist Ca signaling in PFC pyramidal cells with either the dual mGlu/mGlu PAM 16e or 23d demonstrated effects mediated selectively via mGlu.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2021.128342 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Preclinical Investigations Toward Gd-free Molecularly Targeted Dual-Modal, MRI Dynamic (DCE-MRI)/Optical Imaging Contrast Agent for Cardiac Angiosarcoma.
Top Magn Reson Imaging
October 2025
BIOSPACE LAB, Nesles-la-Vallée, France.
Aims: Cardiac tumors are aggressive and asymptomatic in early stages, causing late diagnosis and locoregional metastasis. Currently, the standard of care uses gadolinium-based contrast agents for MRI, and the associated hypersensitivity reactions are a significant concern, such as gadolinium deposition disease. In addition, the proximity of cardiac lesions closer to vital structures complicates surgical interventions.
View Article and Find Full Text PDFDesign of Two Randomized, Placebo-Controlled, Phase 3 Trials of Deucravacitinib, an Oral, Selective, Allosteric TYK2 Inhibitor, in Systemic Lupus Erythematosus.
Adv Ther
September 2025
Bristol Myers Squibb, Princeton, NJ, 08540, USA.
Background And Objectives: Deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor, demonstrated efficacy across the primary endpoint and all key secondary endpoints in the phase 2 PAISLEY SLE trial in patients with active systemic lupus erythematosus (SLE). Here, we describe 2 phase 3 trials [POETYK SLE-1 (NCT05617677), POETYK SLE-2 (NCT05620407)] which will assess the efficacy and safety of deucravacitinib in patients with active SLE. These phase 3 trials have been designed to replicate the successful elements of the phase 2 trial, including its glucocorticoid-tapering strategy and disease activity adjudication.
View Article and Find Full Text PDFGABA receptor availability in clinical high-risk and first-episode psychosis: a [C]Ro15-4513 positron emission tomography study.
Mol Psychiatry
September 2025
Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AB, UK.
Disrupted gamma-aminobutyric acid (GABA) neurotransmission may contribute to the pathophysiology of schizophrenia. Reductions in hippocampal GABAergic neurons have been found in schizophrenia, and increased hippocampal perfusion has been described in schizophrenia and in people at clinical high-risk for psychosis (CHRp). We have also found decreases in hippocampal GABA receptors containing the α5 subunit (GABARα5) in a well-validated neurodevelopmental rat model of relevance for schizophrenia.
View Article and Find Full Text PDFTackling microbial resistance with 4H-chromen-4-one derivatives as a novel class of penicillin binding protein 2a inhibitors.
Bioorg Med Chem
September 2025
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt. Electronic address:
With the continued upsurge of antibiotic resistance and reduced susceptibility to almost all frontline antibiotics, there is a pressing need for the development of new, effective, and safe alternatives. In this study, a scaffold-hopping strategy was utilized to develop a novel class of penicillin-binding protein 2a (PBP2a) inhibitors, centered around a 4H-chromen-4-one core structure. These newly designed compounds demonstrated strong antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and other drug-resistant gram-positive pathogens.
View Article and Find Full Text PDFThe quercetin-serotonin transporter (SERT) connection: a new hope for depression therapy?
Psychopharmacology (Berl)
September 2025
Department of Allied Health Sciences, Chitkara School of Health Sciences, Chitkara University, Punjab, 140401, India.
Quercetin, a naturally occurring flavonoid, has been found to be a potential agent for the treatment of major depressive disorder (MDD), given the complexity of its interaction with the serotonin transporter (SERT). Clinically, quercetin has direct and indirect modulatory effects as opposed to conventional selective serotonin reuptake inhibitors (SSRI), which act mainly by inhibiting SERT after a time delay and communicate with SERT through possible binding location preferences and allosteric processing, while simultaneously controlling its definite expression through anti-inflammatory and antioxidant pathways, such as the NF-kB, AMPK/SIRT-1, and Nrf2-ARE cascades. These processes assist in modifying serotonergic neurotransmission and minimizing oxidative and inflammatory strains, which are the major contributors to the pathophysiology of depression.
View Article and Find Full Text PDF