title: Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning.
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.
authors.affiliation: Institute of Next Generation Healthcare, Mount Sinai Health System, New York, NY, USA.
authors.forename: Khader
authors.initials: K
authors.lastname: Shameer
authors.affiliation: Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Glicksberg
authors.affiliation: Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA.|New York University, New York, NY, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hodos
authors.affiliation: Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA.
authors.forename: Kipp W
authors.initials: KW
authors.lastname: Johnson
authors.affiliation: Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Badgeley
authors.affiliation: Institute of Next Generation Healthcare, Mount Sinai Health System, New York, NY, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Readhead
authors.affiliation: Institute of Next Generation Healthcare, Mount Sinai Health System, New York, NY, USA.
authors.forename: Max S
authors.initials: MS
authors.lastname: Tomlinson
authors.affiliation: Boston College, Boston, MA, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Connor
authors.affiliation: Institute of Next Generation Healthcare, Mount Sinai Health System, New York, NY, USA.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Miotto
authors.affiliation: Institute of Next Generation Healthcare, Mount Sinai Health System, New York, NY, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kidd
authors.affiliation: Clinical Genome Informatics, Icahn Institute of Genetics and Multiscale Biology, Mount Sinai Health System, New York, NY.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Mount Sinai Center for Bioinformatics, Mount Sinai Health System, New York, NY.
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
authors.affiliation: Institute of Next Generation Healthcare, Mount Sinai Health System, New York, NY, USA.|Department of Genetics and Genomic Sciences, Mount Sinai Health System, New York, NY, USA.|Department of Population Health Science and Policy, Mount Sinai Health System, New York, NY, USA.|Director of Biomedical Informatics, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Dudley
mesh_terms: D019295:Computational Biology / Q000379:methods*; D016208:Databases, Factual; D004194:Disease; D055808:Drug Discovery; D058492:Drug Repositioning; D006801:Humans; D017720:Molecular Epidemiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins