National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health , 8600 Rockville Pike, Bethesda, Maryland 20894, United States.
J Chem Inf Model. 2014 Feb 24;54(2):407-18. doi: 10.1021/ci4005354. Epub 2014 Feb 5.
Sixteen FDA-approved drugs were investigated to elucidate their mechanisms of action (MOAs) and clinical functions by pathway analysis based on retrieved drug targets interacting with or affected by the investigated drugs. Protein and gene targets and associated pathways were obtained by data-mining of public databases including the MMDB, PubChem BioAssay, GEO DataSets, and the BioSystems databases. Entrez E-Utilities were applied, and in-house Ruby scripts were developed for data retrieval and pathway analysis to identify and evaluate relevant pathways common to the retrieved drug targets. Pathways pertinent to clinical uses or MOAs were obtained for most drugs. Interestingly, some drugs identified pathways responsible for other diseases than their current therapeutic uses, and these pathways were verified retrospectively by in vitro tests, in vivo tests, or clinical trials. The pathway enrichment analysis based on drug target information from public databases could provide a novel approach for elucidating drug MOAs and repositioning, therefore benefiting the discovery of new therapeutic treatments for diseases.
通过基于检索到的与研究药物相互作用或受研究药物影响的药物靶点的通路分析，研究了 16 种获得美国食品和药物管理局批准的药物，以阐明其作用机制（MOA）和临床功能。蛋白质和基因靶点以及相关通路是通过公共数据库的数据挖掘获得的，包括 MMDB、PubChem 生物测定、GEO DataSets 和 BioSystems 数据库。应用 Entrez E-Utilities，并开发了内部 Ruby 脚本用于数据检索和通路分析，以识别和评估与检索到的药物靶点相关的相关通路。对于大多数药物，都获得了与临床用途或 MOA 相关的通路。有趣的是，一些药物确定了与当前治疗用途不同的其他疾病的通路，并且这些通路通过体外试验、体内试验或临床试验进行了回顾性验证。基于公共数据库中药物靶点信息的通路富集分析可以为阐明药物 MOA 和重新定位提供一种新方法，从而有助于发现治疗疾病的新治疗方法。
