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      PROMISCUOUS: a database for network-based drug-repositioning

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          Abstract

          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 With PROMISCUOUS we provide an exhaustive set of drugs (25 000), including withdrawn or experimental drugs, annotated with drug–protein and protein–protein relationships (21 500/104 000) compiled from public resources via text and data mining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.

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          Most cited references33

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          Cytoscape: a software environment for integrated models of biomolecular interaction networks.

          Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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            The Protein Data Bank.

            The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
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              Drug repositioning: identifying and developing new uses for existing drugs.

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                Author and article information

                Journal
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                January 2011
                January 2011
                10 November 2010
                10 November 2010
                : 39
                : Database issue , Database issue
                : D1060-D1066
                Affiliations
                1Charité – Universitätsmedizin Berlin, Institute for Physiology, Structural Bioinformatics Group, Lindenberger Weg 80, 13125 Berlin, Germany and 2Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla CA 92093-0743, USA
                Author notes
                *To whom correspondence should be addressed. Tel: +49 30 450 540 759; Fax: +49 30 450 540 955; Email: joachim.eichborn@ 123456charite.de
                Correspondence may also be addressed to Robert Preissner. Tel: +49 30 450 540 755; Fax: +49 30 450 540 955; Email: robert.preissner@ 123456charite.de
                Article
                gkq1037
                10.1093/nar/gkq1037
                3013657
                21071407
                d7917d4c-149d-47ce-83c3-eb909b71a448
                © The Author(s) 2010. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 August 2010
                : 29 September 2010
                : 11 October 2010
                Categories
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                Genetics
                Genetics

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