Abstract
Traditional methods for discovery and development of new drugs can be very time-consuming and expensive processes because they include several stages, such as compound identification, pre-clinical and clinical trials before the drug is approved by the U.S. Food and Drug Administration (FDA). Therefore, drug repurposing, namely using currently FDA-approved drugs as therapeutics for other diseases than what they are originally prescribed for, is emerging to be a faster and more cost-effective alternative to current drug discovery methods. In this paper, we have described a three-step in silico protocol for analyzing transcriptomics data using online databases and bioinformatics tools for identifying potentially repurposable drugs. The efficacy of this protocol was evaluated by comparing its predictions with the findings of two case studies of recently reported repurposed drugs: HIV treating drug zidovudine for the treatment of dry age-related macular degeneration and the antidepressant imipramine for small-cell lung carcinoma. The proposed protocol successfully identified the published findings, thus demonstrating the efficacy of this method. In addition, it also yielded several novel predictions that have not yet been published, including the finding that imipramine could potentially treat Severe Acute Respiratory Syndrome (SARS), a disease that currently does not have any treatment or vaccine. Since this in silico protocol is simple to use and does not require advanced computer skills, we believe any motivated participant with access to these databases and tools would be able to apply it to large datasets to identify other potentially repurposable drugs in the future.
Highlights
De novo methods for drug discovery can be incredibly expensive and time consuming
Through experiments performed in mouse models, Fowler et al reported that the drug zidovudine, a Nucleoside Reverse Transcriptase Inhibitor (NRTI) usually used to treat HIV patients, showed strong potential to be used against the untreatable dry form of Age-related Macular
A search for curated studies using the query zidovudine in the BaseSpace Correlation Engine retrieved 10 RNA-expression studies: six studies based on rat experiments and four from experiments done on human data
Summary
A target molecule, such as a gene that is causally linked to a disease, is first identified to initiate the drug discovery process. Scientists systematically screen for small molecules that modulate the target protein-product and carry out a series of optimization steps to improve the efficacy of the lead drug. Periods of animal studies are followed by clinical trials before a drug can be approved for the market by the USA Food and Drug Administration (FDA) (or its counterpart in other countries). This procedure costs four to 12 billion dollars and takes an average of 12 to 17 years to complete [1]. If a promising drug starts to reveal severe side effects during clinical trials, Data 2017, 2, 15; doi:10.3390/data2020015 www.mdpi.com/journal/data
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