Most drugs interact with several pharmacological targets and exhibit complex biological activity spectra. The analysis of these spectra helps to find and optimize new pharmaceutical agents or to identify new applications of investigational and approved drugs (drug repurposing). Since most xenobiotics usually undergo biotransformation in the human body, it is reasonable to consider the biological activity spectra of metabolites during drug R & D.<br/>Web-application MetaTox (http://way2drug.com/mg) generates probable xenobiotics metabolic pathways (represented as a graph with metabolites in nodes) in the human organism. The estimation of the probability of the generated metabolite formation is performed based on an integrated assessment of probabilities of biotransformation reactions and their positions using PASS (http://way2drug.com/passonline) based on the training set consisting of more than 3,500 substrates. The MetaTox user can manually select parameters of a metabolic tree generation, such as its depth and the metabolite formation probability threshold.<br/>We integrated into the MetaTox the possibility of analyzing the probable profiles of biological activity, similar to how it is done in the MetaPASS (http://www.way2drug.com/metapass/). For any compound, an aggregated prediction of the biological activity profile can be obtained, considering the prediction for all its metabolites. Predicted biological activities are divided into seven categories: the mechanisms of action, pharmacological effects, toxicity, and side effects, antitargets, transporters-related interactions, gene expression regulation, and metabolic terms. For any activity, it is possible to obtain a prediction of its presence simultaneously for all compounds from the metabolic graph. Such estimations make it possible to assess the contribution of the parent substance and metabolites to the manifestation of activity.<br/>In the MetaTox, it is possible to create an own graph of any compound's metabolism. When creating nodes of a graph, the user should specify the SMILES of the compound and its chemical names or any other nomination as a label. Each node of the metabolism graph is represented by the structural formula of the corresponding compound. The edges of the metabolism graph should represent the direction of the biotransformation. For the newly created metabolism graph, an analysis of the profile of biological activity taking into account metabolites is also available.

MetaTox 2.0 - freely available online resource for analyzing the probable biological activity spectrum of organic compounds taking into account their possible biotransformation

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.