Τίτλος:
A Web Tool for Ranking Candidate Drugs Against a Selected Disease Based on a Combination of Functional and Structural Criteria
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2019 The Authors
Συγγραφείς:
Karatzas, E.
Minadakis, G.
Kolios, G.
Delis, A.
Spyrou, G.M.
Περιοδικό:
Computational and Structural Biotechnology Journal
Λέξεις-κλειδιά:
Drug products; Filtration, Chemical substance; Cheminformatics; Decision process; Drug development; Drug discovery; Drug ranking; Structural criterion; Structural similarity, Data mining, acute myeloid leukemia; Alzheimer disease; Article; asthma; autoimmune disease; bladder tumor; breast cancer; colorectal cancer; coronary artery disease; data mining; decision making; diabetes mellitus; drug information; drug repositioning; epilepsy; glioblastoma; glioma; human; hydrogen bond; in vitro study; in vivo study; leukemia; liver cell carcinoma; lupus erythematosus; multiple myeloma; multiple sclerosis; neuroblastoma; osteosarcoma; ovary carcinoma; pancreas carcinoma; priority journal; prostate cancer; renal cell carcinoma; rheumatoid arthritis; schizophrenia; squamous cell carcinoma; stomach cancer; transcriptomics; uterine cervix carcinoma
DOI:
10.1016/j.csbj.2019.05.010
