Designed diversity and bioannotated compound libraries for obtaining maximal value from screens in induced pluripotent stem cell-derived cells and other complex biological systems

Recorded On: 02/06/2018

As part of the current resurgence in phenotypic screening, early stage assay systems are becoming increasingly complex in an attempt to better model the disease state and therefore improve translation to the clinic. One downside to this complexity is that it substantially reduces the throughput of such systems, and it is generally not feasible to screen millions of molecules in them as would be common in a more traditional HTS campaign. In response to this constraint we have developed two focused compound collections for use in phenotypic screening projects. The first is a bioannotated or chemogenomic library containing molecules with well-characterised pharmacology, intended for use in repurposing and knowledge-driven target deconvolution approaches. The second is a diverse phenotypic library that attempts to maximise chemical and pharmacological diversity within a compact set of 20,000 compounds, intended as a representative sample of our regular HTS collection. In this presentation the design, construction and annotation of these libraries will be outlined. Some examples of our experiences with screening them in drug discovery projects will then be discussed. Finally, analysis of the extent to which these first generation collections have fulfilled their design criteria to date will be presented, and directions of future enhancements reviewed.

Tim James


With a background in computational chemistry and data analysis, my current focus within the Research Informatics group at Evotec is the area of chemical biology. This includes the design of compound libraries, the analysis of phenotypic screening results and integrating the output from various 'omics technologies.

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