Sánchez-Ruiz, A. & Colmenarejo, G. Updated prediction of aggregators and assay-interfering substructures in food compounds. J. Agric. Food Chem. 69, 15184–15194 (2021).

Article  PubMed  Google Scholar 

Baell, J. B. & Holloway, G. A. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med. Chem. 53, 2719–2740 (2010).

Article  CAS  PubMed  Google Scholar 

David, L. et al. Identification of compounds that interfere with high‐throughput screening assay technologies. ChemMedChem 14, 1795–1802 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bisson, J. et al. Can invalid bioactives undermine natural product-based drug discovery? J. Med. Chem. 59, 1671–1690 (2016).

Article  CAS  PubMed  Google Scholar 

Roche, O. et al. Development of a virtual screening method for identification of “frequent hitters” in compound libraries. J. Med. Chem. 45, 137–142 (2002).

Article  CAS  PubMed  Google Scholar 

Thorne, N., Auld, D. S. & Inglese, J. Apparent activity in high-throughput screening: origins of compound-dependent assay interference. Curr. Opin. Chem. Biol. 14, 315–324 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Coussens, N. P. et al. in Assay Guidance Manual (eds Markossian, S. et al.) 1067–1116 (NCATS, 2020).

Baell, J. & Walters, M. A. Chemistry: chemical con artists foil drug discovery. Nature 513, 481–483 (2014).

Article  CAS  PubMed  Google Scholar 

Coussens, N. P., Auld, D. S., Thielman, J. R., Wagner, B. K. & Dahlin, J. L. Addressing compound reactivity and aggregation assay interferences: case studies of biochemical high-throughput screening campaigns benefiting from the National Institutes of Health Assay Guidance Manual guidelines. SLAS Discov. 26, 1280–1290 (2021).

Article  PubMed  Google Scholar 

Hermann, J. C. et al. Metal impurities cause false positives in high-throughput screening campaigns. ACS Med. Chem. Lett. 4, 197–200 (2013).

Article  CAS  PubMed  Google Scholar 

Chatzopoulou, M. et al. Pilot study to quantify palladium impurities in lead-like compounds following commonly used purification techniques. ACS Med. Chem. Lett. 13, 262–270 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dahlin, J. L. et al. Nuisance compounds in cellular assays. Cell Chem. Biol. 28, 356–370 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Senger, M. R., Fraga, C. A. M., Dantas, R. F. & Silva, F. P. Filtering promiscuous compounds in early drug discovery: is it a good idea? Drug Discov. Today 21, 868–872 (2016).

Article  CAS  PubMed  Google Scholar 

Rothenaigner, I. & Hadian, K. Brief guide: experimental strategies for high-quality hit selection from small-molecule screening campaigns. SLAS Discov. Adv. Sci. Drug Discov. 7, 851–854 (2021).

Article  Google Scholar 

Kallal, L. A. et al. High-throughput screening and triage assays identify small molecules targeting c-MYC in cancer cells. SLAS Discov. 26, 216–229 (2021).

Article  CAS  PubMed  Google Scholar 

Vidler, L. R., Watson, I. A., Margolis, B. J., Cummins, D. J. & Brunavs, M. Investigating the behavior of published PAINS alerts using a pharmaceutical company data set. ACS Med. Chem. Lett. 9, 792–796 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aldrich, C. et al. The ecstasy and agony of assay interference compounds. ACS Cent. Sci. 3, 143–147 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

McCoy, M. A. et al. Biophysical survey of small-molecule β-catenin inhibitors: a cautionary tale. J. Med. Chem. 65, 7246–7261 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dahlin, J. L. & Walters, M. A. How to triage PAINS-full research. ASSAY Drug Dev. Technol. 14, 168–174 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Arrowsmith, C. H. et al. The promise and peril of chemical probes. Nat. Chem. Biol. 11, 536–541 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Newman, D. J. Problems that can occur when assaying extracts to pure compounds in biological systems. Curr. Ther. Res. 95, 100645 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Kenny, P. W. Comment on the ecstasy and agony of assay interference compounds. J. Chem. Inf. Model. 57, 2640–2645 (2017).

Article  CAS  PubMed  Google Scholar 

Seidler, J., McGovern, S. L., Doman, T. N. & Shoichet, B. K. Identification and prediction of promiscuous aggregating inhibitors among known drugs. J. Med. Chem. 46, 4477–4486 (2003).

Article  CAS  PubMed  Google Scholar 

Doak, A. K., Wille, H., Prusiner, S. B. & Shoichet, B. K. Colloid formation by drugs in simulated intestinal fluid. J. Med. Chem. 53, 4259–4265 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Baell, J. B. Feeling nature’s PAINS: natural products, natural product drugs, and pan assay interference compounds (PAINS). J. Nat. Prod. 79, 616–628 (2016).

Article  CAS  PubMed  Google Scholar 

Hendrich, A. B. Flavonoid-membrane interactions: possible consequences for biological effects of some polyphenolic compounds. Acta Pharmacol. Sin. 27, 27–40 (2006).

Article  CAS  PubMed  Google Scholar 

Pawlikowska-Pawlęga, B. et al. Modification of membranes by quercetin, a naturally occurring flavonoid, via its incorporation in the polar head group. Biochim. Biophys. Acta 1768, 2195–2204 (2007).

Article  PubMed  Google Scholar 

Kongkamnerd, J. et al. The quenching effect of flavonoids on 4-methylumbelliferone, a potential pitfall in fluorimetric neuraminidase inhibition assays. SLAS Discov. 16, 755–764 (2011).

Article  CAS  Google Scholar 

McGovern, S. L., Caselli, E., Grigorieff, N. & Shoichet, B. K. Common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J. Med. Chem. 45, 1712–1722 (2002).

Article  CAS  PubMed  Google Scholar 

Capuzzi, S. J., Muratov, E. N. & Tropsha, A. Phantom PAINS: problems with the utility of alerts for pan-assay interference compounds. J. Chem. Inf. Model. 57, 417–427 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cassinelli, G. The roots of modern oncology: from discovery of new antitumor anthracyclines to their clinical use. Tumori J. 102, 226–235 (2016).

Article  CAS  Google Scholar 

Simeonov, A. & Davis, M. I. in Assay Guidance Manual (eds Markossian, S. et al.) 1151–1162 (NCATS, 2004).

Auld, D. S. & Inglese, J. in Assay Guidance Manual (eds Markossian, S. et al.) 1163–1175 (NCATS, 2018).

Dahlin, J. L. & Walters, M. A. The essential roles of chemistry in high-throughput screening triage. Future Med. Chem. 6, 1265–1290 (2014).

Article  CAS  PubMed  Google Scholar 

Jones, P., McElroy, S., Morrison, A. & Pannifer, A. The importance of triaging in determining the quality of output from high-throughput screening. Future Med. Chem. 7, 1847–1852 (2015).

Article  CAS  PubMed  Google Scholar 

Auld, D. S. et al. in Assay Guidance Manual (eds Markossian, S. et al.) 1177–1202 (NCATS, 2017).

Dahlin, J. L., Baell, J. & Walters, M. A. in Assay Guidance Manual (eds. Markossian, S. et al.) 1117-1150 (NCATS, 2015).

Busby, S. A. et al. Advancements in assay technologies and strategies to enable drug discovery. ACS Chem. Biol. 15, 2636–2648 (2020).

Article  CAS  PubMed  Google Scholar 

Holdgate, G., Embrey, K., Milbradt, A. & Davies, G. Biophysical methods in early drug discovery. ADMET DMPK 7, 222–241 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Dahlin, J. L. et al. PAINS in the assay: chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS. J. Med. Chem. 58, 2091–2113 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kitchen, D. B. & Decornez, H. Y. in Small Molecule Medicinal Chemistry: Strategies and Technologies (eds Czechtizky, W. & Hamley, P.) Ch. 7 (Wiley, 2015).

Posner, B. A., Xi, H. & Mills, J. E. J. Enhanced HTS hit selection via a local hit rate analysis. J. Chem. Inf. Model. 49, 2202–2210 (2009).

Article  CAS  PubMed