MetaTox: Web Application for Predicting Structure and Toxicity of Xenobiotics’ Metabolites

Rudik, Anastasia V.; Bezhentsev, Vladislav M.; Дмитриев, А. В.; Druzhilovskiy, Dmitry S.; Lagunin, Alexey; Филимонов, Д. А.; Poroikov, Vladimir

doi:10.1021/acs.jcim.6b00662

Cited by 49 publications

(33 citation statements)

References 28 publications

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“…Ранее нами были подробно описаны методы генерации пути метаболизма и оценки вероятностей образования возможных метаболитов [14,15]. MetaTox использует правила трансформации и рассчитывает вероятность образования метаболитов на основе метода SOMP (Site of Metabolism Prediction) [16], который является модификацией программного алгоритма PASS (прогноз спектра биологической активности для веществ).…”

Section: методикаunclassified

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Xenobiotic toxicity prediction combined with xenobiotic metabolism prediction in the human body

et al. 2019

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The majority of xenobiotics undergo a number of chemical reactions known as biotransformation in human body. The biological activity, toxicity, and other properties of the metabolites may significantly differ from those of the parent compound. Not only xenobiotic itself and its final metabolites produced in large quantities, but the intermediate and final metabolites that are formed in trace quantities, can cause undesirable effects. We have developed a freely available web resource MetaTox (http://www.way2drug.com/mg/) for integral assessment of xenobiotics toxicity taking into account their metabolism in the humans. The generation of the metabolite structures is based on the reaction fragments. The estimates of the probability of the reaction of a certain class and the probability of site of biotransformation are used at the generation of the xenobiotic metabolism pathways. The web resource MetaTox allows researchers to assess the metabolism of compounds in the humans and to obtain assessment of their acute, chronic toxicity, and adverse effects.

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Section: методикаunclassified

“…[16]. На третьем шаге для каждого метаболита рассчитывается оценка вероятности его образования [14].…”

Section: обучающие выборки для прогноза побочных эффектов обучающие вunclassified

Xenobiotic toxicity prediction combined with xenobiotic metabolism prediction in the human body

et al. 2019

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“…30 Other web servers used to predict toxicity are based on the prediction of metabolites formation. This is the case for MetaTox, which can also be used to predict toxicity endpoints, 31 and SOMP, a webservice for the prediction of metabolism by human cytochrome P450. 32 Among various toxicological endpoints, the carcinogenicity of potential drugs is of interest because of its serious effects on human health.…”

Section: Servers To Predict Adme and Toxicity Propertiesmentioning

confidence: 99%

Open chemoinformatic resources to explore the structure, properties and chemical space of molecules

et al. 2017

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“…Необходимо подчеркнуть, что эти рекомендации применимы как к стандартной версии PASS, прогнозирующей несколько тысяч видов биологической активности [36,77], так и к специализированным версиям программы: PASS Targets [78, 79], DIGEP Pred [80,81], PASS CLC Pred [82][83][84], SMP [85,86], SOMP [87,88], RA [89,90], MetaTox [91][92][93], ADVER-Pred [94,95], ROSC-Pred [96,97], KinScreen [98].…”

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Computer-aided prediction of biological activity spectra for chemical compounds: opportunities and limitation

Филимонов

Druzhilovskiy

Lagunin

et al. 2018

BMCRM

135

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An essential characteristic of chemical compounds is their biological activity since its presence can become the basis for the use of the substance for therapeutic purposes, or, on the contrary, limit the possibilities of its practical application due to the manifestation of side action and toxic effects. Computer assessment of the biological activity spectra makes it possible to determine the most promising directions for the study of the pharmacological action of particular substances, and to filter out potentially dangerous molecules at the early stages of research. For more than 25 years, we have been developing and improving the computer program PASS (Prediction of Activity Spectra for Substances), designed to predict the biological activity spectrum of substance based on the structural formula of its molecules. The prediction is carried out by the analysis of structure-activity relationships for the training set, which currently contains information on structures and known biological activities for more than one million molecules. The structure of the organic compound is represented in PASS using Multilevel Neighborhoods of Atoms descriptors; the activity prediction for new compounds is performed by the naive Bayes classifier and the structure-activity relationships determined by the analysis of the training set. We have created and improved both local versions of the PASS program and freely available web resources based on PASS (http://www.way2drug.com). They predict several thousand biological activities (pharmacological effects, molecular mechanisms of action, specific toxicity and adverse effects, interaction with the unwanted targets, metabolism and action on molecular transport), cytotoxicity for tumor and non-tumor cell lines, carcinogenicity, induced changes of gene expression profiles, metabolic sites of the major enzymes of the first and second phases of xenobiotics biotransformation, and belonging to substrates and/or metabolites of metabolic enzymes. The web resource Way2Drug is used by over 18,000 researchers from more than 90 countries around the world, which allowed them to obtain over 600,000 predictions and publish about 500 papers describing the obtained results. The analysis of the published works shows that in some cases the interpretation of the prediction results presented by the authors of these publications requires an adjustment. In this work, we provide the theoretical basis and consider, on particular examples, the opportunities and limitations of computer-aided prediction of biological activity spectra.

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MetaTox: Web Application for Predicting Structure and Toxicity of Xenobiotics’ Metabolites

Cited by 49 publications

References 28 publications

Xenobiotic toxicity prediction combined with xenobiotic metabolism prediction in the human body

Xenobiotic toxicity prediction combined with xenobiotic metabolism prediction in the human body

Open chemoinformatic resources to explore the structure, properties and chemical space of molecules

Computer-aided prediction of biological activity spectra for chemical compounds: opportunities and limitation

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