Computational drug repositioning for ischemic stroke: neuroprotective drug discovery
| Autor: | Andreas Bender, Qingkang Meng, Xiujie Chen, Jingbo Yang, Yan Zhang, Yunong Li |
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| Přispěvatelé: | Li, Yunong [0000-0003-3347-3536], Meng, Qingkang [0000-0001-5006-9370], Chen, Xiujie [0000-0003-2423-8569], Apollo - University of Cambridge Repository |
| Rok vydání: | 2021 |
| Předmět: |
Candidate gene
Dihydropyridines Nifedipine Apoptosis Computational biology Neuroprotection Cell Line 03 medical and health sciences Neuroprotective drug Mice 0302 clinical medicine Neuroprotective Drugs Drug Discovery Medicine Animals Humans Computational analysis 030304 developmental biology Ischemic Stroke Pharmacology 0303 health sciences business.industry Drug Repositioning Computational Biology Drug repositioning Oxidative Stress Neuroprotective Agents Ischemic stroke Molecular Medicine business 030217 neurology & neurosurgery Algorithms Research Article |
| Popis: | Background: A comprehensive approach to drug repositioning will be required to overcome translational hurdles and identify more neuroprotective drugs. Results & methods: Gene Set Enrichment Analysis was applied to identify related pathways and enriched genes. Candidate genes were optimized using ToppGene, ToppGenet and pBRIT. From the perspective of the local structures, gene–domain–substructure–drug relationships were constructed. Using the MCODE algorithm and K-means clustering, 31 functional subnetworks were obtained, and 252 drugs with proposed neuroprotective function were identified. Using computational analysis, 72 substructures with different scores were found to correspond to neuroprotective functions. The protective effects of benidipine and barnidipine were confirmed in vitro. Conclusion: The authors' research has great potential to discover more neuroprotective drugs and obtain more information regarding mechanisms of action and functional substructures. |
| Databáze: | OpenAIRE |
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