Pan-assay interference compounds explained

Pan-assay interference compounds (PAINS) are chemical compounds that often give false positive results in high-throughput screens.^[1] PAINS tend to react nonspecifically with numerous biological targets rather than specifically affecting one desired target.^[2] A number of disruptive functional groups are shared by many PAINS.^{[3] [4]}

While a number of filters have been proposed and are used in virtual screening and computer-aided drug design,^[5] the accuracy of filters with regard to compounds they flag and don't flag has been criticized.^[6]

Common PAINS include toxoflavin, isothiazolones, hydroxyphenyl hydrazones, curcumin, phenol-sulfonamides, rhodanines, enones, quinones, and catechols.^[7]

See also

• Drug discovery

Further reading

• Yang JJ, Ursu O, Lipinski CA, Sklar LA, Oprea TI, Bologa CG . Badapple: promiscuity patterns from noisy evidence . Journal of Cheminformatics . 8 . 29 . 2016 . 27239230 . 4884375 . 10.1186/s13321-016-0137-3 . free .
• BadApple database

Notes and References

1. Baell JB, Holloway GA . New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays . Journal of Medicinal Chemistry . 53 . 7 . 2719–40 . April 2010 . 20131845 . 10.1021/jm901137j . 10.1.1.394.9155 .
2. Baell J, Walters MA . Chemistry: Chemical con artists foil drug discovery . Nature . 513 . 7519 . 481–3 . September 2014 . 25254460 . 10.1038/513481a . 2014Natur.513..481B . free .
3. Dahlin JL, Walters MA . The essential roles of chemistry in high-throughput screening triage . . 6 . 11 . 1265–90 . July 2014 . 25163000 . 4465542 . 10.4155/fmc.14.60 .
4. Baell. JB. Feeling Nature's PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS).. Journal of Natural Products. 25 March 2016. 79. 3. 616–28. 10.1021/acs.jnatprod.5b00947. 26900761.
5. Baell JB, Holloway GA . New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays . Journal of Medicinal Chemistry . 53 . 7 . 2719–40 . April 2010 . 20131845 . 10.1021/jm901137j . 10.1.1.394.9155 .
6. Capuzzi SJ, Muratov EN, Tropsha A . Phantom PAINS: Problems with the Utility of Alerts for Pan-Assay INterference CompoundS . Journal of Chemical Information and Modeling . 57 . 3 . 417–427 . March 2017 . 28165734 . 5411023 . 10.1021/acs.jcim.6b00465 .
7. Chemistry: Chemical con artists foil drug discovery . 513 . 7519 . 481–483 . Nature . Jonathan Baell and Michael A. Walters . September 24, 2014. 10.1038/513481a . 25254460 . free . 2014Natur.513..481B .