Pathway Analysis for Drug Repositioning Based on Public Database Mining

Sixteen FDA-approved
drugs were investigated to elucidate their
mechanisms of action (MOAs) and clinical functions by pathway analysis
based on retrieved drug targets interacting with or affected by the
investigated drugs. Protein and gene targets and associated pathways
were obtained by data-mining of public databases including the MMDB,
PubChem BioAssay, GEO DataSets, and the BioSystems databases. Entrez
E-Utilities were applied, and in-house Ruby scripts were developed
for data retrieval and pathway analysis to identify and evaluate relevant
pathways common to the retrieved drug targets. Pathways pertinent
to clinical uses or MOAs were obtained for most drugs. Interestingly,
some drugs identified pathways responsible for other diseases than
their current therapeutic uses, and these pathways were verified retrospectively
by in vitro tests, in vivo tests, or clinical trials. The pathway
enrichment analysis based on drug target information from public databases
could provide a novel approach for elucidating drug MOAs and repositioning,
therefore benefiting the discovery of new therapeutic treatments for
diseases.