Computer-Aided Xenobiotic Toxicity Prediction Taking into Account their Metabolism in the Human Body
Anastasia V. Rudik, Alexander V. Dmitriev, Alexey A. Lagunin, Sergey M. Ivanov, Dmitry A. Filimonov, Vladimir Poroikov · Biochemistry (Moscow) Supplement Series B Biomedical Chemistry · 2019
Most xenobiotics undergo metabolic conversions in the human body. The biological activity, toxicity, and other properties of such metabolites may significantly differ from those of the parent compounds. Not only xenobiotics and their final metabolites produced in large quantities, but the intermediates and final metabolites formed in trace amounts, can cause undesirable effects. We have developed a freely available web application MetaTox ( http://www.way2drug.com/mg/ ) for integral assessment of xenobiotics toxicity taking into account their metabolism in humans. The generation of the metabolite structures is based on the reaction fragments. The probability estimation of the certain reaction and the probability estimation of the atoms, which are changed during biotransformation, are used for generation of the xenobiotic metabolism pathways. The MetaTox web application assesses metabolism of compounds in humans and evaluates their acute toxicity, specific (cardiotoxicity, hepatotoxicity, nephrotoxicity), and chronic toxicity (carcinogenicity, teratogenicity, mutagenicity, effects on the reproductive system).