ArticleJournal of medicinal chemistry2012
Optimization of a small tropomyosin-related kinase B (TrkB) agonist 7,8-dihydroxyflavone active in mouse models of depression.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 59 citations in OpenAlex.
- A Combined Computational and Experimental Approach to Studying Tropomyosin Kinase Receptor B Binders for Potential Treatment of Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2024Article
- Neuroprotective Action of Coumarin Derivatives through Activation of TRKB-CREB-BDNF Pathway and Reduction of Caspase Activity in Neuronal Cells Expressing Pro-Aggregated Tau Protein.International journal of molecular sciences · 2022Article
- Treating Parkinson's Disease via Activation of BDNF/TrkB Signaling Pathways and Inhibition of Delta-Secretase.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Cellular Membrane Affinity Chromatography Columns to Identify Specialized Plant Metabolites Interacting with Immobilized Tropomyosin Kinase Receptor B.Journal of visualized experiments : JoVE · 2022Article
- Metabolic protection by the dietary flavonoid 7,8-dihydroxyflavone requires an intact gut microbiome.Frontiers in nutrition · 2022Article
- Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome.Nutrients · 2021Article
- 7,8-Dihydroxyflavone Alleviates Anxiety-Like Behavior Induced by Chronic Alcohol Exposure in Mice Involving Tropomyosin-Related Kinase B in the Amygdala.Molecular neurobiology · 2021Article
- Radioligands for Tropomyosin Receptor Kinase (Trk) Positron Emission Tomography Imaging.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Depression as a Neuroendocrine Disorder: Emerging Neuropsychopharmacological Approaches beyond Monoamines.Advances in pharmacological sciences · 2019Review
- Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression.Psychopharmacology · 2018Review
- Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure.PLoS biology · 2017Article
- BDNF - a key transducer of antidepressant effects.Neuropharmacology · 2016Review
- 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders.Translational neurodegeneration · 2016Review
- Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases?Frontiers in psychiatry · 2015Review
- Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation.The international journal of neuropsychopharmacology · 2014Article
- Biochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the TrkB receptor.The Journal of biological chemistry · 2014Article
- Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system.Pharmacological reviews · 2014Review
- Neurotrophic natural products: chemistry and biology.Angewandte Chemie (International ed. in English) · 2014Review
- A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington's disease.PloS one · 2014Article
- Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Structure-activity relationship study shows that the catechol group in 7,8-dihdyroxyflavone, a selective small TrkB receptor agonist, is critical for agonistic activity. To improve the poor pharmacokinetic profiles intrinsic to catechol-containing molecules and to elevate the agonistic effect of the lead compound, we initiated the lead optimization campaign by synthesizing various bioisosteric derivatives. Here we show that the optimized 2-methyl-8-(4'-(pyrrolidin-1-yl)phenyl)chromeno[7,8-d]imidazol-6(1H)-one derivative possesses enhanced TrkB stimulatory activity. Chronic oral administration of this compound significantly reduces the immobility in forced swim test and tail suspension test, two classical antidepressant behavioral animal models, which is accompanied by robust TrkB activation in hippocampus of mouse brain. Further, in vitro ADMET studies demonstrate that this compound possesses the improved features compared to the previous lead compound. Hence, this optimized compound may act as a promising lead candidate for in-depth drug development for treating various neurological disorders including depression.
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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 Socratic graph.