1. Introduction to Metabolizer
ChemAxon User Group Meeting
Budapest 2007
Introduction to Metabolizer
György 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 TransformationsJ I K

4. Predicting Metabolic StabilityF C A r1 r2 r5
Metabolic 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 prediction
All 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) = ? A r1 r2 r5 B C F r5 r7 r3 r5 r3 r4 G H
fast/stable
medium/medium
slow/unstable r5 r7 r8 r1 r3 r4

6. Operating Modes
In 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.

7. Metabolizer GUI development

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 substrates
discovering selected metabolic routes
predicting metabolic stability of given compounds
predicting dominating metabolites of given substrates
toxicity prediction tools based on Metabolizer can consider metabolites and their concentrations
How 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 included
FREE for Academics

9. Acknowledgements Nóra Máté, Zsolt Mohácsi
Plugin system, Chemical Terms Evaluator, Reactor
György T. Balogh, Eszter Papp, Virág Sági Kiss
Human CP450 Xenobiotic Biotransformation Library
István Cseh, Attila Szabó
Reactor Application, Chemical Terms Editor
József Szegezdi, Ferenc Csizmadia
Property predictions, calculations
Szabolcs Csepregi
Substructure searching functions
Miklós Vargyas
Chemical Terms Evaluator