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首页> 外文期刊>BMC Systems Biology >Rational drug repositioning guided by an integrated pharmacological network of protein, disease and drug
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Rational drug repositioning guided by an integrated pharmacological network of protein, disease and drug

机译:蛋白质,疾病和药物的综合药理网络指导合理的药物重新定位

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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/ webcite , http://biomart.i-pharm.org/ webcite ).
机译:背景技术药物发现和开发的过程耗时且昂贵,并且成功的可能性低。因此,人们对将现有药物重新定位为新的医学适应症越来越感兴趣。成功后,此过程可降低失败风险和与新药开发相关的成本。但是,在许多情况下,偶然发现了现有药物的新适应症。因此,显然需要建立合理的药物重新定位方法。结果在这项研究中,我们建立了一个名为“ PharmDB”的数据库,该数据库整合了与疾病适应症,药物开发和相关蛋白质以及从各种既有数据库中提取的已知相互作用相关的数据。为了探索PharmDB中已知药物与关注疾病的联系,我们设计了共享邻域评分(SNS)算法。为了促进对三方(Drug-Protein-Disease)网络的探索,我们开发了一种名为phExplorer的图形数据可视化软件程序,该程序可让我们以交互和动态的方式浏览PharmDB数据。我们通过确定高血压药物苯并噻嗪(TBZT)潜在的应用来诱导肺癌细胞死亡,从而验证了这种基于知识的工具套件。结论通过将集成的三方数据库PharmDB与共享邻域评分(SNS)算法相结合,我们开发了一个知识平台,可以合理地识别已知的FDA批准药物的新适应症,可以使用手动管理方法针对特定项目进行定制。 PharmDB中的数据是开放访问的,可以使用phExplorer轻松浏览并通过BioMart网络服务(http://www.i-pharm.org/ webcite,http://biomart.i-pharm.org/ webcite)进行访问。

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