Pan-assay interference compounds

Cartoon depiction of a representative pan-assay interference compound. The drug-like molecule specifically interacts with target B, but the PAINS-like compound non-specifically interacts with multiple targets

Pan-assay interference compounds, also referred to as PAINS in the assay or simply PAINS, are chemical compounds that are often false positives in high-throughput screens.[1] PAINS tend to nonspecifically react with numerous biological targets rather than specifically affecting one desired target.[2] A number of disruptive functional groups are shared by many PAINS.[2][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]

See also

References

  1. ↑ Dahlin JL, Nissink JW, Strasser JM, Francis S, Higgins L, Zhou H, Zhang Z, Walters MA (March 2015). "PAINS in the assay: chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS". Journal of Medicinal Chemistry. 58 (5): 2091–113. doi:10.1021/jm5019093. PMC 4360378. PMID 25634295.
  2. 1 2 Baell J, Walters MA (September 2014). "Chemistry: Chemical con artists foil drug discovery". Nature. 513 (7519): 481–3. Bibcode:2014Natur.513..481B. doi:10.1038/513481a. PMID 25254460.
  3. ↑ Dahlin JL, Walters MA (July 2014). "The essential roles of chemistry in high-throughput screening triage". Future Medicinal Chemistry. 6 (11): 1265–90. doi:10.4155/fmc.14.60. PMC 4465542. PMID 25163000.
  4. ↑ Baell, JB (25 March 2016). "Feeling Nature's PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS)". Journal of Natural Products. 79 (3): 616–28. doi:10.1021/acs.jnatprod.5b00947. PMID 26900761.
  5. ↑ Baell JB, Holloway GA (April 2010). "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. doi:10.1021/jm901137j. PMID 20131845.
  6. ↑ Capuzzi SJ, Muratov EN, Tropsha A (March 2017). "Phantom PAINS: Problems with the Utility of Alerts for Pan-Assay INterference CompoundS". Journal of Chemical Information and Modeling. 57 (3): 417–427. doi:10.1021/acs.jcim.6b00465. PMC 5411023. PMID 28165734.

Further reading

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


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