Institute of Next Generation Healthcare, Mount Sinai Health System, New York, NY, USA.
Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA.
Brief Bioinform. 2018 Jul 20;19(4):656-678. doi: 10.1093/bib/bbw136.
Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health outcomes. However, the rapid increase in drug development cost demands innovative and sustainable drug discovery approaches. Drug repositioning, the discovery of new or improved therapies by reevaluation of approved or investigational compounds, solves a significant gap in the public health setting and improves the productivity of drug development. As the number of drug repurposing investigations increases, a new opportunity has emerged to understand factors driving drug repositioning through systematic analyses of drugs, drug targets and associated disease indications. However, such analyses have so far been hampered by the lack of a centralized knowledgebase, benchmarking data sets and reporting standards. To address these knowledge and clinical needs, here, we present RepurposeDB, a collection of repurposed drugs, drug targets and diseases, which was assembled, indexed and annotated from public data. RepurposeDB combines information on 253 drugs [small molecules (74.30%) and protein drugs (25.29%)] and 1125 diseases. Using RepurposeDB data, we identified pharmacological (chemical descriptors, physicochemical features and absorption, distribution, metabolism, excretion and toxicity properties), biological (protein domains, functional process, molecular mechanisms and pathway cross talks) and epidemiological (shared genetic architectures, disease comorbidities and clinical phenotype similarities) factors mediating drug repositioning. Collectively, RepurposeDB is developed as the reference database for drug repositioning investigations. The pharmacological, biological and epidemiological principles of drug repositioning identified from the meta-analyses could augment therapeutic development.
全球人口增长和传染病（寨卡病毒）、多药耐药病原体、耐药性癌症（顺铂耐药性卵巢癌）和慢性病（高血压）的出现导致疾病负担不断增加，这就需要有效的治疗方法来改善健康状况。然而，药物开发成本的快速增长要求采用创新和可持续的药物发现方法。药物再定位，即通过重新评估已批准或正在研究的化合物来发现新的或改进的疗法，解决了公共卫生环境中的一个重大差距，并提高了药物开发的生产力。随着药物再定位研究的数量增加，通过对药物、药物靶点和相关疾病的系统分析来了解驱动药物再定位的因素，出现了一个新的机会。然而，到目前为止，这种分析受到缺乏集中的知识库、基准数据集和报告标准的阻碍。为了满足这些知识和临床需求，我们在这里展示了 RepurposeDB，这是一个由重新定位药物、药物靶点和疾病组成的集合，这些数据是从公共数据中收集、索引和注释的。RepurposeDB 结合了 253 种药物（小分子[74.30%]和蛋白药物[25.29%]）和 1125 种疾病的信息。使用 RepurposeDB 数据，我们确定了介导药物再定位的药理学（化学描述符、理化性质和吸收、分布、代谢、排泄和毒性特性）、生物学（蛋白质结构域、功能过程、分子机制和途径交叉交谈）和流行病学（共享的遗传结构、疾病共病和临床表型相似性）因素。总的来说，RepurposeDB 被开发为药物再定位研究的参考数据库。从荟萃分析中确定的药物再定位的药理学、生物学和流行病学原则可以增强治疗的发展。
