ArticleACS chemical biology2013
Chemical interrogation of the neuronal kinome using a primary cell-based screening assay.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 39 citations in OpenAlex.
- How many kinases are druggable? A review of our current understanding.The Biochemical journal · 2023Article
- Phenotypic drug discovery: recent successes, lessons learned and new directions.Nature reviews. Drug discovery · 2022Review
- Compounds co-targeting kinases in axon regulatory pathways promote regeneration and behavioral recovery after spinal cord injury in mice.Experimental neurology · 2022Article
- Novel adult cortical neuron processing and screening method illustrates sex- and age-dependent effects of pharmaceutical compounds.Scientific reports · 2022Article
- Phenotypic Screening Following Transcriptomic Deconvolution to Identify Transcription Factors Mediating Axon Growth Induced by a Kinase Inhibitor.SLAS discovery : advancing life sciences R & D · 2021Article
- In vitro modeling of dendritic atrophy in Rett syndrome: determinants for phenotypic drug screening in neurodevelopmental disorders.Scientific reports · 2020Article
- Cell death assays for neurodegenerative disease drug discovery.Expert opinion on drug discovery · 2019Review
- Scaffold Ranking and Positional Scanning Identify Novel Neurite Outgrowth Promoters with Nanomolar Potency.ACS medicinal chemistry letters · 2018Article
- High-throughput screen for compounds that modulate neurite growth of human induced pluripotent stem cell-derived neurons.Disease models & mechanisms · 2018Article
- The mTOR Substrate S6 Kinase 1 (S6K1) Is a Negative Regulator of Axon Regeneration and a Potential Drug Target for Central Nervous System Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- High content analysis in amyotrophic lateral sclerosis.Molecular and cellular neurosciences · 2017Review
- In vitro models of axon regeneration.Experimental neurology · 2017Review
- RegenBase: a knowledge base of spinal cord injury biology for translational research.Database : the journal of biological databases and curation · 2016Article
- Exploiting kinase polypharmacology for nerve regeneration.Neural regeneration research · 2016Article
- Magnetic Alignment of Microelements Containing Cultured Neuronal Networks for High-Throughput Screening.Journal of biomolecular screening · 2015Article
- Phenotypic assays to identify agents that induce reactive gliosis: a counter-screen to prioritize compounds for preclinical animal studies.Assay and drug development technologies · 2015Article
- Rational Polypharmacology: Systematically Identifying and Engaging Multiple Drug Targets To Promote Axon Growth.ACS chemical biology · 2015Article
- Protection and Repair After Spinal Cord Injury: Accomplishments and Future Directions.Topics in spinal cord injury rehabilitation · 2015Article
- cJun promotes CNS axon growth.Molecular and cellular neurosciences · 2014Article
- Kinase-mediated signaling cascades in mood disorders and antidepressant treatment.Journal of neurogeneticsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
A fundamental impediment to functional recovery from spinal cord injury (SCI) and traumatic brain injury is the lack of sufficient axonal regeneration in the adult central nervous system. There is thus a need to develop agents that can stimulate axon growth to re-establish severed connections. Given the critical role played by protein kinases in regulating axon growth and the potential for pharmacological intervention, small molecule protein kinase inhibitors present a promising therapeutic strategy. Here, we report a robust cell-based phenotypic assay, utilizing primary rat hippocampal neurons, for identifying small molecule kinase inhibitors that promote neurite growth. The assay is highly reliable and suitable for medium-throughput screening, as indicated by its Z'-factor of 0.73. A focused structurally diverse library of protein kinase inhibitors was screened, revealing several compound groups with the ability to strongly and consistently promote neurite growth. The best performing bioassay hit robustly and consistently promoted axon growth in a postnatal cortical slice culture assay. This study can serve as a jumping-off point for structure activity relationship (SAR) and other drug discovery approaches toward the development of drugs for treating SCI and related neurological pathologies.
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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.