The ECT solution includes an extended version of the TOPKAT toxicity prediction tool.
TOPKAT is an established in-silico method for assessing toxicity prediction of organic compounds. TOPKAT can help assess environmental fate, ecotoxicity, toxicity, mutagenicity, and reproductive/developmental toxicity of chemicals.
TOPKAT technology is currently used to:
- Optimise therapeutic ratios of lead compounds
- Prioritise promising compounds for further development/investment
- Evaluate intermediates, metabolites and pollutants
- Screen compounds generated via HTS systems
- Assess pharmaceutical, commercial, industrial and agricultural chemical products for potential safety problems
- Set dose-ranges for animal assays
The ECT solution gives users access to both standard, established TOPKAT models as well as advanced features that allow extending and tuning the predictions based on supplemental experimental data or research efforts leveraging focused types of chemistry. For example:
- replace or augment the original experimental data with experimental results from proprietary compounds.
- recreate the statistical correlations with a focused set of structures that represents a specific chemistry of interest.
TOPKAT toxicity models are based on highly cleaned and consistent experimental data from open literature, statistically robust and validated QSAR relationships. It includes tools for examining and validating the assessment, by using univariate analysis and Accelrys patented Optimum Prediction Space* method. Similarity searching for structures within the training set for the predictive model available, warns users if data is outside of the optimum predictive space for higher confidence in results provided.
- Rodent Carcinogenicity (as a sex and species specific endpoint based on either the NTP dataset or the FDA dataset)
- Weight of Evidence Carcinogenicity
- Carcinogenic Potency TD50
- Ames Mutagenicity
- Developmental Toxicity Potential (DTP)
- Rat Oral LD50
- Rat Maximum Tolerated Dose
- Rat Inhalational LC50
- Rat Chronic Oral LOAEL
- Skin Irritancy
- Skin Sensitization (GPMT)
- Ocular Irritancy
- Aerobic Biodegradability
- Fathead Minnow LC50
- Daphnia magna EC50
- VlogP
In addition to established TOPKAT models, the ECT solution provides the ability to re-build models are built with updated training sets and advanced modelling techniques available within Pipeline Pilot. New training data can be added to improve the coverage of the model space. Statistical methods for those extensible models include Bayesian Models for classification models, and Partial Least Squares (PLS) Models for regression models.