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Improving the safety assessment of chemicals and drug candidates by the integrating bioinformatics and chemoinformatics

Pognan, Francois and Steger-Hartmann, Thomas (2018) Improving the safety assessment of chemicals and drug candidates by the integrating bioinformatics and chemoinformatics. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7843


The application of read-across and in silico tools for regulatory decision making has been limited for pharmaceutical compounds to the assessment of genotoxic impurity. In contrast, the broad availability of toxicity data for industrial chemicals has triggered regulatory frameworks for read-across (e.g. ECHA read-across assessment framework), software tools and public databases for an automated process of gap filling for safety assessment framework. This review provides an overview of the currently existing read-across approaches for chemicals and pharmaceutical compounds highlighting particularly the different requirements in the safety assessment of these two fields.
The biggest hurdle for establishing preclinical safety databases for pharma compounds are the unwillingness to share proprietary data and lack of published data sets. In a consortial approach thirteen pharmaceutical companies, eleven academic partners and six small to medium size enterprises (SMEs) of the bioinformatics sector joined forces over the last seven years within the European Innovative Medicines Initiative project eTOX ("electronic toxicity") to design and implement a strategy for leveraging these preclinical data and sharing them across project partners. The eTOX database has evolved as the largest preclinical toxicity database for drugs and drug candidates and currently contains more than 1900 different chemical structures and more than 8000 in vivo toxicity study data. Use cases based on chemical or biological similarity are presented. It can be foreseen that the development and application of such databases for drugs or drug candidates will in the future also cross-fertilize the read-across and in silico assessment of industrial or consumer chemicals particularly as soon as human safety data from clinical trials are integrated, too.

Item Type: Article
Date Deposited: 30 Mar 2018 00:45
Last Modified: 30 Mar 2018 00:45