High throughput screening (HTS) is an established method for identifying target specific lead molecules for drug discovery. However, it is known that many compounds exhibit non-specific and interfering effects on either the target or the assay technology; these compounds are known as <i>pan assay interference compounds (PAINS)</i>. Many methods have been proposed to limit the occurrence of PAINS in high throughput assays. Here, we demonstrate the use of a library of annotated compounds of known nuisance mechanisms for two purposes: 1) Optimization of assay conditions to reduce the prevalence of nuisance compounds which are hits in the assay and 2) Focus HTS triaging assays on the most pernicious nuisance mechanism for that particular assay. The collection consists of compounds that exhibit well-characterized nuisance effects, such as aggregation, redox compounds, metal contaminants and compounds with known PAINS structures. We have profiled the nuisance set against &gt;50 assays including enzymatic, biochemical binding, cellular, biophysical binding and nuisance mechanism assays and will discuss collective findings.

Reduction and efficient triage of nuisance compounds in HTS hit sets using a library of known nuisance compounds

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