Karatzas Evangelos, Minadakis George, Kolios George, Delis Alex, Spyrou George M
Department of Informatics and Telecommunications, University of Athens, 15703 Athens, Greece.
The Cyprus Institute of Neurology and Genetics, 6 International Airport Avenue, Nicosia, 2370, Cyprus.
Comput Struct Biotechnol J. 2019 Jun 29;17:939-945. doi: 10.1016/j.csbj.2019.05.010. eCollection 2019.
Drug repurposing techniques allow existing drugs to be tested against diseases outside their initial spectrum, resulting in reduced cost and eliminating the long time-frames of new drug development. In silico drug repurposing further speeds up the process either by proposing drugs suitable to invert the transcriptomic profile of a disease or by indicating drugs based on their common targets or structural similarity with other drugs with similar mode of action. Such methods usually return a number of potential repurposed drugs that need to be tested against the disease in in vitro, pre-clinical and clinical studies. Thus, it is crucial to have a more sophisticated candidate drug ranking in order to start testing from the most promising chemical substances. As a means to enhance the above decision process, we present CoDReS (Composite Drug Reranking Scoring), a drug (re-)ranking web-based tool, which combines an initial drug ranking (i.e. repurposing score or hypothesis/potentiality score) with a functional score of each drug considered in conjunction with the disease under study as well as with a structural score derived from potential drugability violations. Furthermore, a structural similarity clustering is applied on the considered drugs and a handful of structural exemplars are suggested for further in vitro and in vivo validation. The user is able to filter the results further, through structural similarity examination of the candidate drugs with drugs that have failed against the queried disease where related clinical trials have been carried out. CoDReS is publicly available online at http://bioinformatics.cing.ac.cy/codres.
药物重新利用技术允许对现有药物针对其初始谱以外的疾病进行测试，从而降低成本并消除新药开发的长时间框架。计算机辅助药物重新利用通过提出适合逆转疾病转录组谱的药物，或者基于其共同靶点或与具有相似作用模式的其他药物的结构相似性来指明药物，进一步加速了这一过程。此类方法通常会返回许多潜在的重新利用药物，这些药物需要在体外、临床前和临床研究中针对该疾病进行测试。因此，为了从最有前景的化学物质开始测试，拥有更精细的候选药物排名至关重要。作为增强上述决策过程的一种手段，我们展示了CoDReS（复合药物重新排名评分），这是一种基于网络的药物（重新）排名工具，它将初始药物排名（即重新利用分数或假设/潜力分数）与结合所研究疾病考虑的每种药物的功能分数以及从潜在成药违规中得出的结构分数相结合。此外，对所考虑的药物应用结构相似性聚类，并建议少量结构范例用于进一步的体外和体内验证。用户能够通过对候选药物与在相关临床试验中针对所查询疾病失败的药物进行结构相似性检查来进一步筛选结果。CoDReS可在网上公开获取，网址为http://bioinformatics.cing.ac.cy/codres。
