Latent Hit Identification in Primary Screening Data with Compound Set Enrichment

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SELECTBIO

High Throughput Screening (HTS) has become widely used in the pharmaceutical industry to deliver chemistry entry points for drug discovery programs. Despite the high costs associated with HTS, analysis of the structure activity data generated at this initial stage of the drug discovery process is still very restricted. Very often hits are defined as compounds whose activity exceeds a certain threshold value in a given assay. This strategy leads to identification of individual active compounds. However, the main goal of HTS is actually the identification of an active chemical series, rather than just individual active compounds. Thus, we have developed a new method, called Compound Set Enrichment to analyse primary screening data. The method employs a scaffold based compound classification, in conjunction with the Kolmogorov-Smirnov statistic to assess the overall activity of a compound scaffold. This method, initially designed to identify a series of active compounds also enables identification of weak active compounds (potentially latent hits) that were missed before. To highlight this characteristic, we’ll show how CSE can be used to analyse assays with only weak active compounds. Promotion examples of weak active compounds into very active compounds (latent hit promotion) will be shown.