Poster 18: Identification of (Latent) Hit Series in Primary Screening DataAnsgar Schuffenhauer1, Thibault Varin1, Marie-Cecile Didiot1, Christian N. Parker1
|1Novartis Institues for BioMedical Research|
|The main goal of high-throughput screening (HTS) is to identify active chemical series rather than just individual active compounds. In light of this goal, a new method (called compound set enrichment) to identify active chemical series from primary screening data is proposed. The method employs the scaffold tree compound classification in conjunction with the Kolmogorov-Smirnov statistic to assess the overall activity of a compound set sharing a common scaffold. The scaffolds are thereby defined by rule based methods, such as the scaffold tree or scaffold network. As there is not hard activity cut-off for individual compounds applied in compound set enrichment, this method is able to uncover “latent hits” in primary screening data, which would be missed by cut-off based methods. This capability is demonstrated retrospectively on a screening set from PubChem. A prospective case study was done on a medium throughput assay for the identification of compounds modulating protein translation directed from the Internal Ribosome Entry Site (IRES) of the Encephalomyocarditis Virus (EMCV) genomic RNA. Latent hit series were identified, which could then be expanded with SAR by inventory to obtain more potent hits.|
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