The advent of high throughput screening brought a new problem for the medicinal chemist: false positives. These are compounds that appear active in an assay but rather than giving a useful mode of inhibition are actually interfering with the assay technology. Such compounds can be a huge resource sink and distraction for chemists and biologists, so across Pharma chemists developed rules for removing them. One of the highest impact sets of rules is Baell and Holloway’s Pan Assay INterference or PAINS set. However as with any set of rules they’re highly controversial as obviously excluding a compound right at the start of a programme can make a significant impact. The debate about their use rages on.
“New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays” Baell and Holloway: J. Med. Chem. 2010, 53, 2719–2740
And for the debate about the filters to use and their selection:
Tropsha:. J. Chem. Inf. Model. 2017, 57, 417−427
Kenny: J. Chem. Inf. Model. 2017, 57, 2640−2645
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