PROMISCUOUS: a database for network-based drug-repositioning

The procedure of drug approval is time-consuming, costly and risky. Accidental findings regarding multi-specificity of approved drugs led to block-busters in new indication areas. Therefore, the interest in systematically elucidating new areas of application for known drugs is rising. Furthermore, the knowledge, understanding and prediction of so-called off-target effects allow a rational approach to the understanding of side-effects. With PROMISCUOUS we provide an exhaustive set of drugs (25 000), including withdrawn or experimental drugs, annotated with drug–protein and protein–protein relationships (21 500/104 000) compiled from public resources via text and data mining including manual curation. Measures of structural similarity for drugs as well as known side-effects can be easily connected to protein–protein interactions to establish and analyse networks responsible for multi-pharmacology. This network-based approach can provide a starting point for drug-repositioning. PROMISCUOUS is publicly available at http://bioinformatics.charite.de/promiscuous.

[1]  P. Bork,et al.  A side effect resource to capture phenotypic effects of drugs , 2010, Molecular systems biology.

[2]  Stefan Günther,et al.  SuperPred: drug classification and target prediction , 2008, Nucleic Acids Res..

[3]  Philip E. Bourne,et al.  Drug Discovery Using Chemical Systems Biology: Repositioning the Safe Medicine Comtan to Treat Multi-Drug and Extensively Drug Resistant Tuberculosis , 2009, PLoS Comput. Biol..

[4]  E. Schadt,et al.  Integrative genomics and drug development. , 2009, Pharmacogenomics.

[5]  Baris E. Suzek,et al.  The Universal Protein Resource (UniProt) in 2010 , 2009, Nucleic Acids Res..

[6]  Philip E. Bourne,et al.  Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors , 2009, PLoS Comput. Biol..

[7]  Michael J. Keiser,et al.  Predicting new molecular targets for known drugs , 2009, Nature.

[8]  Kiyoko F. Aoki-Kinoshita,et al.  From genomics to chemical genomics: new developments in KEGG , 2005, Nucleic Acids Res..

[9]  Andy Gray,et al.  The Selection and Use of Essential Medicines. , 2015, World Health Organization technical report series.

[10]  M Day.  The bitterest pill , 2007, BMJ : British Medical Journal.

[11]  H. Kitano.  A robustness-based approach to systems-oriented drug design , 2007, Nature Reviews Drug Discovery.

[12]  Mathias Dunkel,et al.  SuperDrug: a conformational drug database , 2005, Bioinform..

[13]  A. Krantz.  Diversification of the drug discovery process , 1998, Nature Biotechnology.

[14]  P. Bork,et al.  Drug Target Identification Using Side-Effect Similarity , 2008, Science.

[15]  Bruce L. Booth,et al.  Quest for the best , 2003, Nature Reviews Drug Discovery.

[16]  Van V. Brantner,et al.  Estimating the cost of new drug development: is it really 802 million dollars? , 2006, Health affairs.

[17]  Ralf Herwig,et al.  ConsensusPathDB—a database for integrating human functional interaction networks , 2008, Nucleic Acids Res..

[18]  Hans-Werner Mewes,et al.  CORUM: the comprehensive resource of mammalian protein complexes , 2007, Nucleic Acids Res..

[19]  I. Kola,et al.  Can the pharmaceutical industry reduce attrition rates? , 2004, Nature Reviews Drug Discovery.

[20]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[21]  Antje Chang,et al.  BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009 , 2008, Nucleic Acids Res..

[22]  T. Ashburn,et al.  Drug repositioning: identifying and developing new uses for existing drugs , 2004, Nature Reviews Drug Discovery.

[23]  Des Spence.  The bitterest pill , 2007, BMJ : British Medical Journal.

[24]  I. Kola,et al.  The State of Innovation in Drug Development , 2008, Clinical pharmacology and therapeutics.

[25]  Robert B. Russell,et al.  SuperTarget and Matador: resources for exploring drug-target relationships , 2007, Nucleic Acids Res..

[26]  Michael Schroeder,et al.  SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions , 2009, Nucleic Acids Res..

[27]  María Martín,et al.  The Universal Protein Resource (UniProt) in 2010 , 2010 .

[28]  E. Kunkel.  Systems biology in drug discovery , 2004, Nature Biotechnology.

[29]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[30]  G. Klebe,et al.  Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition. , 2004, Journal of medicinal chemistry.

[31]  David S. Wishart,et al.  DrugBank: a knowledgebase for drugs, drug actions and drug targets , 2007, Nucleic Acids Res..

[32]  Otis Gospodnetic,et al.  Lucene in Action , 2004 .