Rational drug repositioning guided by an integrated pharmacological network of protein, disease and drug.
Rational drug repositioning guided by an integrated pharmacological network of protein, disease and drug.
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以蛋白质、疾病和药物的综合药理学网络为指导的合理药物重新定位
DOI：
10.1186/1752-0509-6-80
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发表时间：
2012-07-02
影响因子：
--
通讯作者：
Kim S
中科院分区：
文献类型：
--
作者：
Lee HS;Bae T;Lee JH;Kim DG;Oh YS;Jang Y;Kim JT;Lee JJ;Innocenti A;Supuran CT;Chen L;Rho K;Kim S
背景药物的发现和开发过程既耗时又昂贵，而且成功的概率很低。因此，人们对为新的医学适应症重新定位现有药物的兴趣与日俱增。当成功时，这个过程降低了失败的风险和与新药开发相关的成本。然而，在许多情况下，现有药物的新适应症是偶然发现的。结果在本研究中，我们建立了一个名为“PharmDB”的数据库，该数据库集成了与疾病适应症、药物开发和相关蛋白质相关的数据，以及从各种已建立的数据库中提取的已知相互作用。为了探索已知药物与PharmDB中感兴趣的疾病之间的联系，我们设计了共享邻居评分(SNS)算法。为了便于探索药物-蛋白质-疾病三方网络，我们开发了一个图形化的数据可视化软件程序phExplorer，它允许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)诱导肺癌细胞死亡的潜在应用来验证这个基于知识的工具包。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FDA批准的已知药物的新适应症，可以使用手动管理根据特定项目进行定制。PharmDB中的数据是开放访问的，可以使用phExplorer轻松地进行浏览，并可以通过BioMart Web服务(http://www.i-pharm.org/，http://biomart.i-pharm.org/)访问。
BackgroundThe 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 withde novodrug 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.ResultsIn 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.ConclusionsBy 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/ ).
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影响因子：
8.6
作者：
Pastor-Satorras, R;Vázquez, A;Vespignani, A
通讯作者：
Vespignani, A
影响因子：
56.9
作者：
Campillos, Monica;Kuhn, Michael;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
--
作者：
HAVARD, CWH;WOOD, PHN
通讯作者：
WOOD, PHN
影响因子：
4.3
作者：
Hidalgo CA;Blumm N;Barabási AL;Christakis NA
通讯作者：
Christakis NA
影响因子：
14.9
作者：
Ceol A;Chatr Aryamontri A;Licata L;Peluso D;Briganti L;Perfetto L;Castagnoli L;Cesareni G
通讯作者：
Cesareni G