MetaSite

MetaSite Site of metabolism prediction for CYP2C9 and CYP3A4 and others www.moldiscovery.com... 

Cruciani et al. [92] have developed the program Metasite for the prediction of the site of oxidative metabolism by CYP450 enzymes. Metasite uses GRID molecular interaction fields to fingerprint both structures of CYP450s (from homology models or crystal structures) and test substrates and then matches the fields. Zhou et al. [93] showed that Metasite was able to correctly predict the site(s) of metabolism 78% of the time for 227 CYP3A4 substrates. Caron et al. [94] used Metasite to predict the oxidative metabolism of seven statins. 

A metasite with full and changing MEDLINE search engines List of free sites... 

The protein factor in MetaSite is based on homology models of the CYP450s, but it offers the possibility for the user to introduce any CYP450 structure. Several analyses have been done comparing the results obtained using the crystal structures and the homology models of the cytochromes. 

The evaluation of the impact of the different crystal structures on the prediction of the site of metabolism by the MetaSite methodology without reactivity correction has been considered. In this case one can conclude that overall the rate of good prediction (number of experimentally determined sites of metabolism among the first three solutions predicted by MetaSite) is similar for the different structures. Nevertheless, there is only a moderate overlap between the compounds that are well predicted by each crystal structure, and a combination of all structures usually yield higher prediction rates. When using the reactivity correction, the difference between the prediction rates for each crystal structure is reduced, suggesting a diminishing rate of the crystal structure used for the analysis. 

Vianello, R. (2005) MetaSite understanding metabolism in human cytochromes from the perspective of the chemist. Journal of Medicinal Chemistry, 48, 6970-6979. 

MetaSite Understanding CYP Antitarget Modeling for Early Toxicity Detection... 

The MetaSite procedure is fully automated and does not require any user assistance. All the work can be submitted and handled in a batch computation. The flexible MIFs for CYP structures and those for the UGT structures obtained from the GRID package are precomputed and stored. Once the structures of the... 

The overall procedure is called MetaSite (site of metabolism prediction) [32]. The M IF calculations, pharmacophoric recognition, descriptor handling, similarity computation, reactivity computation, inhibition and subselectivity are calculated automatically once the ligand compound(s) is(are) provided. The complete calculation is performed in few seconds in IRIX Linux or Windows environments. 

Cruciani, G., Carosati, E., De Boeck, B., Ethirajulu, K., Mackie, C., Howe, T. and Vianello, R. (2005) MetaSite understanding metabolism in human cytochromes from the perspective of the chemist. Journal of Medicinal Chemistry, 48, 6970-6979. 

The CYPs as Antitarget Enzymes 278 The UGTs as Antitarget Enzymes 279 The MetaSite Technology 282 Mechanism-Based Inhibitors 285 Phase II Metabolism by UGTs 287 The Flowchart of the Overall Method 287 Conclusions 289 Software Package 290 References 290... 

MetaSite Molecular Discovery 185 http //www.moldiscovery.com/index.php... 

Finally MIFs will be used to explain cytochrome P450 (CYP) 3A4 inhibition. The use of METASITE in understanding and predicting the site of metabolism... 

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