Metabolic predicting

Databases and Rule-Based Approaches for Metabolism Prediction... 

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

DATABASES AND RULE-BASED APPROACHES FOR METABOLISM PREDICTION... 

Simulation methods have also been developed that include physiologically based pharmacokinetic modeling (PBPK) and methods such as Cloe PK, OMPPPlus, GastroPlus , SimCYP , and others [122] that are described elsewhere in this book. It is likely that the computational metabolism predictions could be integrated with these to assist in deriving more accurate predictions of human pharmacokinetic parameters. 

In conclusion, it is likely that computational approaches for metabolism prediction will continue to be developed and integrated with other algorithms for pharmaceutical research and development, which may in turn ultimately aid in their more widespread use in both industry and academia. Such models may already be having some impact when integrated with bioanalytical approaches to narrow the search for possible metabolites that are experimentally observed. Software that can be updated by the user as new metabolism information becomes available would also be of further potential value. The held of metabolism prediction has therefore advanced rapidly over the past decade, and it will be important to maintain this momentum in the future as the hndings from crystal structures for many discrete metabolic enzymes are integrated with the diverse types of computational models already derived. 

Anari MR, Sanchez RI, Bakhtiar R, Franklin RB, Baillie TA. Integration of knowledge-based metabolic predictions with liquid chromatography data-dependent tandem mass spectrometry for drug metabolism studies application to studies on the biotransformation of indinavir. Anal Chem 2004 76 823-32. 

Greene N, Judson PN, Langowski JJ, Marchant CA. Knowledge-based expert systems for toxicity and metabolism prediction DEREK, StAR and METEOR. SAR QSAR Environ Res 1999 10 299-314. 

The virtual compounds can be input into metabolism prediction programs, such as Metabolexpert [30] or Meteor [31], to identify principal pathways of expected drug metabolism. 

Factors That Influence the Site of Metabolism Prediction by Cytochrome P450s... 

Another approach to knowledge-based metabolic predictions is SPORCalc [29]. 

Afzelius, L., Arnby, C.H., Broo, A., Carlsson, L., Isaksson, C., Jurva, U., Kjellander, B., Kolmodin, K., Nilsson, K., Raubacher, F. and Weidolf, L. (2007) State-of-the-art tools for computational site of metabolism predictions comparative analysis, mechanistical insights, and future applications. Drug Metabolism Reviews, 39 (1), 61-86. 

Zamora, I., Afzelius, L. and Crudani, G. (2003) Predicting drug metabolism a site of metabolism prediction tool applied to the cytochrome P450 2 C9. Journal of Medicinal Chemistry, 46, 2313—2324. 

The predicted metabolites are also the starting point for the phase II metabolic prediction, to find where glucuronidation could occur. All the probable metabolites obtained from CYP metabolism reactions are submitted to a possible phase II reaction catalyzed by UGTs, using the UGT structure(s) as a template. The accessibility component is computed in the UGTcavity to prioritize glucuronic acid transfer. The final metabolite structures are then reported in graphical output or saved to a file. 

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. 

G. Predicting drug metabolism a site of metabolism prediction tool applied to the... 

QSAR Approaches for Metabolism Prediction the P450 Isozyme... 

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