CETSA based toxicology profiling - a new way to identify liabilities in drug discovery projects

Purpose and goal

The aim of this project was to establish a foundation for a database composed of protein-based markers of toxicological effects derived from known toxic compounds. Such database should be an asset for Pelago Bioscience and make up a new area of service offers. During the project we have improved our processes and the way in which we collect data, which in turn allowed profiling of far more compounds than originally anticipated. We now have a database that is continuously growing, currently some 200 compounds are included, that we use to compare and explain data in customer projects.

Expected results and effects

In the original application we aimed at profiling 10 compounds, but now it is clear that data from such number of compounds would be of limited use. After profiling some 200 compounds we can apply more sophisticated statistics and apply pattern recognition by artificial intelligence. As the database grows, we envision how we hopefully can move from pure comparison of molecular profiles into more refined prediction of a molecule’s cellular and clinical effects. In addition to the database, this project has resulted in a scientific publication.

Planned approach and implementation

The project contained six work packages, where data collection was carried out in parallel to analysis and addition of new compounds to the list. We performed a detailed first profiling of 12 compounds to test whether the data from our final format would be able to provide a similar level of understanding. Having confirmed this, we proceeded to data production and quality assessments. The first large global analysis was done half-way through the compound list and gave us the confirmation to proceed. The market and patent-analysis has been carried out throughout the project’s lifetime.