DEREK for Windows

Finally, results from DEREK clearly suggest that all the selected PFCs are non-carcinogenic compounds. It is important to underline that in our application of DEREK a compound was considered non-carcinogenic if the response was Nothing to report, although this is not the intended use of the Nothing to report output of the Derek for Windows software [50]. 

Marchant CA, Briggs KA, Long A (2008) In silico tools for sharing data and knowledge on toxicity and metabolism Derek for Windows, Meteor, and Vitic. Toxicol Mech Methods 18 177-187... 

To help establish the relevance of a skin sensitization alert from DEREK for Windows, the system incorporates reasoning that allows the determination of skin permeability coefficients (log Kp values) according to the algorithm developed by Potts and Guy (1990). DEREK for Windows derives log Kp from the logarithm of the octanol/water partition coefficient (log Kow) using the following equation (Moriguchi et al., 1992) ... 

DEREK for Windows calculates log Kp in cm/h using a modified Potts and Guy equation ... 

These additional parameters enable DEREK for Windows to indicate to the user whether a skin sensitization hazard alert given is likely to be expressed. In the example of citronellal given above, DEREK for Windows indicates that the hazard of skin sensitization is plausible. In another example, diacetyl-diperoxyadipic acid, alert 406 — skin sensitization (diacyl peroxide) is fired as highlighted in Figure 9.3. 

All the results described above can be exported from DfW to other applications by generating a DEREK for Windows report in either rich text (rtf), tab delimited text, or modified sd file format (Figure 3). 

Fig. 2. Screen-print from the DEREK for Windows prediction for the compound 2-methyl-4-[(2-methylphenyl)azo]benzenamine (a) imported structure, (b) prediction results window, (c) alert description window, (d) example compounds window...

Fig. 3. Report from the DEREK for Windows prediction for the compound 2-methyl-4-[(2-methylphenyl)azo]benzenamine...

DEREK for Windows. Version 7. User Guide (2003) Lhasa Limited, Department of Chemistry, University of Leeds, Leeds, UK... 

TABLE 11.3. Summary of in silica predictive toxicological evaluations of onchidal by Derek for Windows and MDL-QSAR... 

Derek for Windows Mutagenicity - plausible Alert 302 a,P-unsaturated aldehyde Skin sensitization - plausible Alert 425 Enol ether Alert 479 a,P-unsaturated aldehyde... 

FIGURE 11.3. The Derek for Windows version 10.0.2 (DfW) prediction for onchidal under default processing contraints. 

Matthews, E.J., Kruhlak, N.L., Benz, R.D., Contrera, J.F. (2008). Combined use of MC4PC, MDL-QSAR, BioEpisteme, Leadscope PDM, and Derek for Windows software to achieve high-performance, high-confidence, model of action-based predictions of chemical carcinogenesis in rodents. Toxicol. Mech. Meth. 18 189-206. 

In silico tools make a significant contribution to the SAR-based early identification of potential toxicity. An increasing volume of published preclinical and clinical toxicity data are collected and used to build structure-related searchable databases. These expert knowledge databases can analyze chemical structures and match them with potential mechanisms of toxicity. DEREK for Windows (Lhasa Ltd.)39 is one of such broadly used knowledge-based expert systems to provide toxicology alerts for new compounds. Although certainly not comprehensive, numerous efforts have been made to predict hepatotoxicity. Recently,... 

Although DEREK is still available from the LHASA group at Harvard University, it has not be updated in recent times, having been superseded by Derek for Windows from Lhasa Limited. 

Derek for Windows [12] uses structural alerts to trigger warnings about potential toxicity, but its predictions are controlled by a reasoning system [13,14,15] based on the Logic of Argumentation. The system manipulates rules of the general form... 

More generally, the question of what to do about programs that make predictions that are neither quantitative nor binary has yet to be answered satisfactory. The usual measures of performance require that a program either generate numerical estimates of potency or make a binary prediction—active or inactive. A program such as Derek for Windows may predict that activity is plausible, probable, equivocal, doubted, and so on. There is a case for treating equivocal as a prediction that activity will be borderline, but if activity is predicted to be plausible, is that a yes If it is, then what does probable mean ... 

Langton K, Marchant CA. Improvements to the Derek for Windows prediction of chromosome damage. Toxicol Lett 2005 158(1 ) S36-S37. 

Langton K, Patlewicz GY, Long A, Marchant CA, Basketter DA (2006) Structure-activity relationships for skin sensitization recent improvements to Derek for Windows. Contact Dermatitis 55 342-347... 

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