SESSION 4: Drug metabolism prediction

Combining measurement and computation for the prediction of xenobiotic metabolism

Prof Johannes Kirchmair


Center for Bioinformatics, University of Hamburg


Junior professor


Nils-Ole Friedrich and Johannes Kirchmair


Metabolism of small organic molecules can yield metabolites with substantially different physicochemical and biological properties [1].

Consequently, understanding metabolism is of immediate relevance to the safety and efficacy of drugs, cosmetics, nutritional supplements and agrochemicals. Recent advances in experimental and computational approaches allow the generation of a fairly complete picture of xenobiotic metabolism. The integration of methods of both domains holds an enormous potential for synergy, which however is not fully harnessed yet [2].

In this contribution we assess the scope and limitations of the leading experimental and computational technologies for metabolism prediction, with a focus on the prediction of sites of metabolism and metabolite structures. We discuss current strategies for improving the prediction accuracy and relevance of in vitro and in silico models and present recent case studies illustrating the synergies created by using these approaches in tandem.

[1] Kirchmair, J.; Howlett, A.; Peironcely, J.; Murrell, D. S.; Williamson, M. J.; Adams, S. E.; Hankemeier, T.; van Buren, L.; Duchateau, G.; Klaffke, W.; Glen, R. C. How do metabolites differ from their parent molecules and how are they excreted? Journal of Chemical Information and Modeling 2013, 53, 354-367.
[2] Kirchmair, J.; Göller, A. H.; Lang, D.; Kunze, J.; Testa, B.; Wilson, I. D.; Glen, R. C.; Schneider, G., Predicting drug metabolism: Experiment and/or computation? Nature Reviews Drug Discovery 2015, 14, 387-404.