News & Publications


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New Publication: A Novel QSAR Model of Salmonella Mutagenicity and Its Application in the Safety Assessment of Drug Impurities

A new paper co-authored by scientists at US FDA and Prous Institute for Biomedical Research describes the development and validation of a QSAR model to predict Salmonella t. mutagenicity (Ames assay outcome) of pharmaceutical impurities using Prous Institute SYMMETRY SM, the world’s first integrated in silico solution for drug discovery and safety screening.  Data was sourced from public benchmark databases with known Ames assay mutagenicity outcomes for 7300 chemical (57% mutagens).  Internal cross-validation yielded 84 +/- 1% sensitivity, 81 +/- 1% specificity, 83 +/- 1% concordance and 79 +/- 1% negative predictivity.

The model’s prediction performance characteristics were shown to be highly satisfactory for protecting public health, given the consistency in accurately predicting true positives (sensitivity) and true negatives (specificity) using different external validation test sets from reliable data sources, and a high coverage of 96% for drug impurities indicating broad applicability domain. The results from the studies provide confidence in the reliability, stability, and practical utility of the predictions for identification of chemical mutagens and non-mutagens.

The paper also describes the successful analysis with Symmetry of previously recognized hard-to-predict compounds, which other computational toxicology software packages have been unable to predict correctly thus far (Sutter et al., 2013).  

The model is suitable to support risk evaluation of potentially mutagenic compounds under ICH M7, along with expert human decision-making.

A novel QSAR model of Salmonella mutagenicity and its application in the safety assessment of drug impurities; Antoni Valencia, Josep Prous, Oscar Mora, Nakissa Sadrieh, Luis Valerio Jr.; Toxicology and Applied Pharmacology, Volume 273, Issue 3, 15 December 2013, Pages 427–434