Series of screening compounds with high hit rates for the exploration of multi-target activities and assay interference

Abstract

Aim: Generation of a database of analog series (ASs) with high assay hit rates for the exploration of assay interference and multi-target activities of compounds. Methodology: ASs were computationally extracted from extensively tested screening compounds with high hit rates. Data: A total of 6941 ASs were assembled comprising 14,646 unique compounds that were tested in a total of 1241 different assays covering 426 specified targets. These ASs were organized and prioritized on the basis of different activity and assay frequency criteria. All ASs and associated information are made available in an open access deposition. Next steps: The large set of ASs will be further analyzed computationally and from a chemical perspective to identify assay interference compounds and candidates for exploring target promiscuity. In drug discovery, compounds are tested in high-throughput screening assays for desired biological activities. Unfortunately, some test compounds that are not specifically active give false-positive (artificial) activity signals in assays, which are difficult to recognize. However, other compounds can bind specifically to multiple targets and hence give true activity signals in multiple assays. To help distinguish between artifacts and true activities, we have systematically identified series of analogs (i.e., structurally closely related compounds) that are active with unusually high frequency across biological assays. Herein, we describe these data and make them freely available for follow-up analysis.