ArticleBioorganic & medicinal chemistry letters2015
Cyclopropyl-containing positive allosteric modulators of metabotropic glutamate receptor subtype 5.
Article in Bioorganic & medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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
9 citing papers in PubMed, 11 citations in OpenAlex.
- Computational Ligand-Binding Site Prediction.Advances in experimental medicine and biology · 2026Review
- Design, Synthesis, and Antimicrobial Activity of Amide Derivatives Containing Cyclopropane.Molecules (Basel, Switzerland) · 2024Article
- Modeling Epac1 interactions with the allosteric inhibitor AM-001 by co-solvent molecular dynamics.Journal of computer-aided molecular design · 2020Article
- Identification and characterization of fragment binding sites for allosteric ligand design using the site identification by ligand competitive saturation hotspots approach (SILCS-Hotspots).Biochimica et biophysica acta. General subjects · 2020Article
- Optimization and Evaluation of Site-Identification by Ligand Competitive Saturation (SILCS) as a Tool for Target-Based Ligand Optimization.Journal of chemical information and modeling · 2019Article
- Estimation of relative free energies of binding using pre-computed ensembles based on the single-step free energy perturbation and the site-identification by Ligand competitive saturation approaches.Journal of computational chemistry · 2017Article
- Mixed-Probe Simulation and Probe-Derived Surface Topography Map Analysis for Ligand Binding Site Identification.Journal of chemical theory and computation · 2017Article
- Driving Structure-Based Drug Discovery through Cosolvent Molecular Dynamics.Journal of medicinal chemistry · 2016Review
- Virtual Screening and Molecular Dynamics Study of Potential Negative Allosteric Modulators of mGluR1 from Chinese Herbs.Molecules (Basel, Switzerland) · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Positive allosteric modulators (PAMs) binding to the transmembrane (TM) domain of metabotropic glutamate receptor 5 (mGluR5) are promising therapeutic agents for psychiatric disorders and traumatic brain injury (TBI). Novel PAMs based on a trans-2-phenylcyclopropane amide scaffold have been designed and synthesized. Facilitating ligand design and allowing estimation of binding affinities to the mGluR5 TM domain was the novel computational strategy, site identification by ligand competitive saturation (SILCS). The potential protective activity of the new compounds was evaluated using nitric oxide (NO) production in BV2 microglial cell cultures treated with lipopolysaccharide (LPS), and the toxicity of the new compounds tested using a cell viability assay. One of the new compounds, 3a, indicated promising activity with potency of 30 μM, which is 4.5-fold more potent than its lead compound 3,3'-difluorobenzaldazine (DFB), and showed no detectable toxicity with concentrations as high as 1000 μM. Thus this compound represents a new lead for possible development as treatment for TBI and related neurodegenerative disorders.
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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.