Presentation on theme: "Introduction to Metabolizer"— Presentation transcript:
1 Introduction to Metabolizer ChemAxon User Group MeetingBudapest 2007Introduction to MetabolizerGyörgy Pirok
2 The Biotransformation Library The current version of the biotransformation library contains 183 Reactor compatible generic phase I. human xenobiotic CP450 biotransformatons.
3 Metabolite Generation with Competing Transformations JIK
4 Predicting Metabolic Stability FCAr1r2r5Metabolic stability prediction will be based on the prediction of the speed of transforming reactions.If a substrate is destroyed by at least one fast reaction, it is not stable!Three levels of biotransformation speed/priority predictionAll generic biotransformations are classified into speed categories (very fast, fast, medium, very slow, slow)If the examples of a biotransformation have reaction speed data contains measurements, they can be used to predict the transformation speed of the current substrate by a special reaction similarity computation.In case of some oxidative biotransformations a speed prediction can be calculated directly from the substrate.
5 Predicting Dominating Metabolites Dominating metabolites are those that are accumulated in higher concetrations than others. They are produced by fast transformation routes and destroyed by slow ones.Dominating metabolite prediction is more complex than metabolic stability prediction.f(x) = ?Ar1r2r5BCFr5r7r3r5r3r4GHfast/stablemedium/mediumslow/unstabler5r7r8r1r3r4
6 Operating ModesIn exhaustive metabolism mode all possible metabolites are enumerated until a given step count or a termination condition defined in Chemical Terms. Dominating metabolites can be color highlighted. Danger of combinatorial explosion.Selective metabolism mode generates only dominating metabolites. This reduces the chance of a combinatorial explosion and provides a much smaller metabolite set.Users can drive the Metaboliser in manual mode as well to modify the prediction or focus on the interesting pathways.
8 Summary What will Metabolizer be? What will it be good for? Metabolizer will be a metabolic biotransformation prediction tool based on the Reactor engine and other technologies.What will it be good for?generating all possible metabolites of given substratesdiscovering selected metabolic routespredicting metabolic stability of given compoundspredicting dominating metabolites of given substratestoxicity prediction tools based on Metabolizer can consider metabolites and their concentrationsHow will I be able to access it?Off the shelf (Metabolizer Application)Integrating into applications (Java/.NET API, Oracle Cartidge)Human CP450 phase I. xenobiotic biotranformation library includedFREE for Academics
9 Acknowledgements Nóra Máté, Zsolt Mohácsi Plugin system, Chemical Terms Evaluator, ReactorGyörgy T. Balogh, Eszter Papp, Virág Sági KissHuman CP450 Xenobiotic Biotransformation LibraryIstván Cseh, Attila SzabóReactor Application, Chemical Terms EditorJózsef Szegezdi, Ferenc CsizmadiaProperty predictions, calculationsSzabolcs CsepregiSubstructure searching functionsMiklós VargyasChemical Terms Evaluator