Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning. (15th February 2017)

• Record Type: Journal Article
• Authors: Shameer, Khader; Glicksberg, Benjamin S; Hodos, Rachel; Johnson, Kipp W; Badgeley, Marcus A; Readhead, Ben; Tomlinson, Max S; O'Connor, Timothy; Miotto, Riccardo; Kidd, Brian A; Chen, Rong; Ma'ayan, Avi; Dudley, Joel T
• Is Part Of: Briefings in bioinformatics. Volume 19:Number 4(2018:Jul.)
• Page Start: 656
• Page End: 678
• Publication Date: 2017-02-15
• Subjects: precision medicine -- drug repositioning -- translational bioinformatics -- drug development -- drug discovery -- precision pharmacology -- systems pharmacology; Genetics -- Data processing -- Periodicals; Molecular biology -- Data processing -- Periodicals; Genomes -- Data processing -- Periodicals; 572.80285
• DOI: 10.1093/bib/bbw136
• Languages: English
• ISSNs: 1467-5463

Abstract

Abstract: Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health outcomes. However, the rapid increase in drug development cost demands innovative and sustainable drug discovery approaches. Drug repositioning, the discovery of new or improved therapies by reevaluation of approved or investigational compounds, solves a significant gap in the public health setting and improves the productivity of drug development. As the number of drug repurposing investigations increases, a new opportunity has emerged to understand factors driving drug repositioning through systematic analyses of drugs, drug targets and associated disease indications. However, such analyses have so far been hampered by the lack of a centralized knowledgebase, benchmarking data sets and reporting standards. To address these knowledge and clinical needs, here, we present RepurposeDB, a collection of repurposed drugs, drug targets and diseases, which was assembled, indexed and annotated from public data. RepurposeDB combines information on 253 drugs [small molecules (74.30%) and protein drugs (25.29%)] and 1125 diseases. Using RepurposeDB data, we identified pharmacological (chemical descriptors, physicochemical features and absorption, distribution, metabolism, excretion and toxicity properties), biological (protein domains, functional process, molecular mechanisms and pathway cross talks) and epidemiological (shared genetic architectures, disease comorbidities and clinical phenotype similarities) factors mediating drug repositioning. Collectively, RepurposeDB is developed as the reference database for drug repositioning investigations. The pharmacological, biological and epidemiological principles of drug repositioning identified from the meta-analyses could augment therapeutic development.