TOPKAT

A number of commercial expert systems have been applied to screen drug libraries. For instance, DEREK, TOPKAT, MultiCASE, and many other systems all have possibilities in this regard. However, it should be noted that for broad screening only compounds with toxicity associated with them can be identified, and hence these are very crude measures of hazard assessment. The use of expert systems to screen libraries is fraught with dangers, not least that no performance statistics are available for these systems being used for such an application. It is also highly probable that the vast majority of predic-... 

There are two commercially available expert systems that rely on a statistical approach TOPKAT, which was developed by Health Designs Inc. but is now owned by Accelrys [18], and CASE/MultiCASE, developed at Case Western University [31]. 

There are a growing number of tools to assess applicability domain, and a number of expert systems, for example, TOPKAT and MultiCASE, have their own measures of fit. These need to be developed and their application to larger drug libraries demonstrated. 

Prival, M.. Evaluation of the TOPKAT system for predicting the carcinogenicity of chemicals. Environ. Mol. Mutagen. 2001, 37, 55-69. 

I. Y. Assessment of the sensitivity of the computational programs DEREK, TOPKAT, and MCASE in the prediction of the genotoxicity of pharmaceutical molecules. Environ. Mol. Mutagen. 2004,... 

VLOGP (v 3.1) model from the Toxicity Predicfion (TOPKAT) protocol in Discovery Studio 1.7, http //www. accelrys.com /products /topkat. 

TOPKAT Quantitative structure toxicity relationship (QSTR) models for assessing various measures of toxicity... 

TOPKAT Toxicity prediction http www.accelrys.com/products/... 

Enslein, K., Blake, B. W., Tomb, M. E. and Borgstedt. H. H. (1986). In Vitro Toxicology 1, 33-44. TOPKAT Program, Health Designs Incorporated, 183 East Main St., Rochester, New York, USA. 

TOPKAT toxicology prediction tool Health Designs Inc. (HDI)... 

There is a number of commercial software programs, such as TOPKAT [21], MULTICASE [22], HazardExpert [23], and DEREK [24], They address a number of endpoints. In some cases, they only give SAR models, most typically they predict a continuous value. 

TOPKAT comprises 13 QSAR models and data from which these models are derived (rabbit skin irritation). Compounds and data were collected from national and international journals as well as U.S. government sources and total some 1258 compounds. The chemicals are grouped into five class specific models, heteroaromatic and multiple benzenes, alicylics, single benzenes, and two classes of acrylics. Each model applies to a specific class of chemicals and is further subdivided into two or three groups based on severity. 

TOPKAT Automated Rule-Induction Systems Accelrys Ltd. www.accelrys.com/products/topkat/ mutagenicity, teratogenicity, membrane irritation, neurotoxicity, and other effects Carcinogenicity,... 

ARI systems make quantitative predictions, for example, by providing a probability value of carcinogenicity being induced by a molecule or a quantitative prediction of an acute toxicity. Two widely used ARI systems are Toxicity Prediction by Komputer-Assisted Technology (TOPKAT) (Enslein, 1988 Enslein et al 1994) and Multiple Computer Automated Structure Evaluation... 

Danish Environmental Protection Agency Mutagenicity, carcinogenicity, skin sensitization, acute toxicity, aquatic toxicity M-CASE and TOPKAT models (see Table 19.5) Tyle et al. (2001)... 

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