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dc.contributor.authorYilancioglu, Kaan
dc.contributor.authorWeinstein, Zohar B.
dc.contributor.authorMeydan, Cem
dc.contributor.authorAkhmetov, Azat
dc.contributor.authorToprak, Isil
dc.contributor.authorDurmaz, Arda
dc.contributor.authorLossifov, Ivan
dc.contributor.authorKazan, Hilal
dc.contributor.authorRoth, Frederick P.
dc.contributor.authorCokol, Murat
dc.date.accessioned2014-10-22T12:56:56Z
dc.date.available2014-10-22T12:56:56Z
dc.date.issued2014-05-08
dc.identifier.citationYilancioglu K., Meydan C., Weinstein Z.B., Cokol M., Akhmetov A., Lossifov I., Kazan H., Roth F.P., Cokol M. (2014), Target-independent Prediction of Drug Synergies Using only Drug Lipophilicity, Journal of Chemical Information and Modeling,tr_TR
dc.identifier.issn1549-960x
dc.identifier.urihttp://earsiv.uskudar.edu.tr/xmlui/handle/123456789/338
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/pubmed/25026390
dc.description.abstractPhysicochemical properties of compounds have been instrumental in selecting lead compounds with increased drug-likeness. However, the relationship between physicochemical properties of constituent drugs and the tendency to exhibit drug interaction has not been systematically studied. We assembled physicochemical descriptors for a set of antifungal compounds (“drugs”) previously examined for interaction. Analyzing the relationship between molecular weight, lipophilicity, H-bond donor, and H-bond acceptor values for drugs and their propensity to show pairwise antifungal drug synergy, we found that combinations of two lipophilic drugs had a greater tendency to show drug synergy. We developed a more refined decision tree model that successfully predicted drug synergy in stringent cross-validation tests based on only lipophilicity of drugs. Our predictions achieved a precision of 63% and allowed successful prediction for 58% of synergistic drug pairs, suggesting that this phenomenon can extend our understanding for a substantial fraction of synergistic drug interactions. We also generated and analyzed a large-scale synergistic human toxicity network, in which we observed that combinations of lipophilic compounds show a tendency for increased toxicity. Thus, lipophilicity, a simple and easily determined molecular descriptor, is a powerful predictor of drug synergy. It is well established that lipophilic compounds (i) are promiscuous, having many targets in the cell, and (ii) often penetrate into the cell via the cellular membrane by passive diffusion. We discuss the positive relationship between drug lipophilicity and drug synergy in the context of potential drug synergy mechanisms.tr_TR
dc.language.isoengtr_TR
dc.relation.ispartofseriesSCI-expanded;
dc.relation.isversionofdx.doi.org/10.1021/ci500276xtr_TR
dc.subjectDrugtr_TR
dc.subjectDrug Synergiestr_TR
dc.subjectDrug Lipophilicitytr_TR
dc.titleTarget-Independent Prediction of Drug Synergies Using Only Drug Lipophilicitytr_TR
dc.typeArticletr_TR
dc.relation.journalJournal of Chemical Information and Modelingtr_TR
dc.contributor.departmentÜsküdar Üniversitesi, Sağlık Meslek Yüksek Okulu, Biyomedikal Cihaz Teknolojisitr_TR
dc.contributor.authorIDTR115885tr_TR


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