Resources & Training

Abstract:
Metabolites can play an important role in adverse effects of parent drug (or other xenobiotic) compounds. During the EU-H2020 OpenRiskNet project, several partners (VU Amsterdam, HHU/HITeC Hamburg, Uppsala University, JGU Mainz) have worked together on making methods and tools available within the OpenRiskNet platform for metabolite and site-of-metabolism (SOM) prediction. For that purpose we have integrated ligand-based metabolite predictors (e.g., MetPred, FAME 3, SMARTCyp) and protein-structure and -dynamics based models to predict SOMs of Cytochrome P450 (CYP450) substrates. CYP450s metabolize ~75% of the currently marketed drugs and their active-site shape and plasticity often play an important role in determining the substrate's SOM. To facilitate the combined use of the metabolite prediction approaches and their outcomes, we made Jupyter notebooks available that gather and visualize results from the integrated services. Here we illustrate the possible added value of their combined use in the context of a pilot study on SOM prediction for compounds with known metabolite-associated toxicity. Finally we shortly discuss related work from our laboratory, on predicting Cytochrome P450 binding affinity prediction.

Abstract:
Case studies are used to test and evaluate the solutions provided by OpenRiskNet to the predictive toxicology and risk assessment community especially regarding the usability of the developed APIs and the interoperability layer.

Abstract:
Besides new and improved in vitro methods, in silico plays a major role in the endeavor to reach the 3R goals of replacement, reduction and refinement in both toxicodynamics and biokinetics and especially in the interplay with the first mentioned methods in forming integrated approaches to testing and assessment (IATA) and integrated testing strategies (ITS). However, for the most efficient usage of these methods and making them available to all stakeholder, these tools need to be available and accessible not necessarily in an open (not in the sense of free of charge but of open, interpretable and reproducible science), harmonized and interoperable way. This session will present international approaches and platforms providing discovery services and repositories for predictive-toxicology and risk-assessment software solutions and related disciplines, activities to harmonize the description, access and usage of these and ways to combine them into workflows for more complex analysis and modeling task.