A systems-level analysis of drug-target-disease associations for drug repositioning
| Autor: | Kayleigh Rutherford, Nicola Mulder, Gaston K. Mazandu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Drug media_common.quotation_subject 0206 medical engineering Drug target 02 engineering and technology Computational biology Disease Biology Biochemistry 03 medical and health sciences Drug Discovery Genetics Humans Molecular Biology media_common Molecular interactions Drug discovery Systems Biology Drug Repositioning Computational Biology Proteins General Medicine Drug repositioning 030104 developmental biology Genetics Population Drug development Vitamin b6 020602 bioinformatics |
| Zdroj: | Briefings in functional genomics. 17(1) |
| ISSN: | 2041-2657 |
| Popis: | Drug repositioning is the process of finding new therapeutic uses for existing, approved drugs-a process thathas value when considering the exorbitant costs of novel drug development. Several computational strategies exist as a way to predict these alternative applications. In this study, we used datasets on: (1) human biological drug targets and (2) disease-associated genes and, based on a direct functional interaction between them, searched for potential opportunities for drug repositioning. From the set of 1125 unique drug targets and their 88 490 interactions with disease-associated genes, 30 drug targets were analyzed and (3) discussed in detail for the purpose of this article. The current indications of the drugs thattarget them were validated through the interactions, and new opportunities for repositioning were predicted. Among the set of drugs for potential repositioning werebenzodiazepines for the treatment of autism spectrum disorders; nortriptyline for the treatment of melanoma, glioma and other cancers; and vitamin B6 in prevention of spontaneous abortions and cleft palate birth defects. Special emphasis was also placed on those new potential indications that pertained to orphan diseases-these are diseases whose rarity means that development of novel treatment is not financially viable. This computational drug repositioning approach uses existing information on drugs and drug targets, and insights into the genetic basis of disease, as a means to systematically generate the most probable new uses for the drugs on offer, and in this way harness their true therapeutic power. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|