title: Rational drug repositioning guided by an integrated pharmacological network of protein, disease and drug.
abstract: BACKGROUND
  The process of drug discovery and development is time-consuming and costly, and the probability of success is low. Therefore, there is rising interest in repositioning existing drugs for new medical indications. When successful, this process reduces the risk of failure and costs associated with de novo drug development. However, in many cases, new indications of existing drugs have been found serendipitously. Thus there is a clear need for establishment of rational methods for drug repositioning.
  
  
  RESULTS
  In this study, we have established a database we call "PharmDB" which integrates data associated with disease indications, drug development, and associated proteins, and known interactions extracted from various established databases. To explore linkages of known drugs to diseases of interest from within PharmDB, we designed the Shared Neighborhood Scoring (SNS) algorithm. And to facilitate exploration of tripartite (Drug-Protein-Disease) network, we developed a graphical data visualization software program called phExplorer, which allows us to browse PharmDB data in an interactive and dynamic manner. We validated this knowledge-based tool kit, by identifying a potential application of a hypertension drug, benzthiazide (TBZT), to induce lung cancer cell death.
  
  
  CONCLUSIONS
  By combining PharmDB, an integrated tripartite database, with Shared Neighborhood Scoring (SNS) algorithm, we developed a knowledge platform to rationally identify new indications for known FDA approved drugs, which can be customized to specific projects using manual curation. The data in PharmDB is open access and can be easily explored with phExplorer and accessed via BioMart web service (http://www.i-pharm.org/, http://biomart.i-pharm.org/).
authors: Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul, Korea.
authors: Hee Sook
authors: HS
authors: Lee
authors: Taejeong
authors: T
authors: Bae
authors: Ji-Hyun
authors: JH
authors: Lee
authors: Dae Gyu
authors: DG
authors: Kim
authors: Young Sun
authors: YS
authors: Oh
authors: Yeongjun
authors: Y
authors: Jang
authors: Ji-Tea
authors: JT
authors: Kim
authors: Jong-Jun
authors: JJ
authors: Lee
authors: Alessio
authors: A
authors: Innocenti
authors: Claudiu T
authors: CT
authors: Supuran
authors: Luonan
authors: L
authors: Chen
authors: Kyoohyoung
authors: K
authors: Rho
authors: Sunghoon
authors: S
authors: Kim
mesh_terms: D000465:Algorithms; D001581:Benzothiadiazines / Q000627:therapeutic use; D019295:Computational Biology / Q000379:methods*; D062313:Databases, Pharmaceutical; D004194:Disease; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
chemical_list: D001581:Benzothiadiazines; D011506:Proteins; C004463:benzothiazide