How to Triage PAINS-Full Research.
Nonspecific bioactivity and assay artifacts have gained increasing attention in recent years. This focus has arisen primarily from the publication of a set of chemical substructures, termed pan assay interference compounds (PAINS), which are associated with promiscuous bioactivity and assay interference in real and virtual high-throughput screening (HTS) campaigns. Despite an increasing awareness in the HTS and medicinal chemistry communities about the liabilities of these compounds, articles featuring PAINS and PAINS-like compounds are still being published. In this perspective, we describe some of the factors we believe are driving this resource-sapping trend. We also provide what we hope are helpful insights that may lead to the earlier recognition of these generally nontranslatable compounds, thus preventing the propagation of PAINS-full costly research.
1 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Mayo Clinic College of Medicine , Rochester, Minnesota.|2 Medical Scientist Training Program, Mayo Clinic College of Medicine, Mayo Clinic College of Medicine , Rochester, Minnesota.
Jayme L
JL
Dahlin
3 Institute for Therapeutics Discovery and Development, University of Minnesota , Minneapolis, Minnesota.
Michael A
MA
Walters
D016477:Artifacts; D002626:Chemistry, Pharmaceutical; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D015394:Molecular Structure; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D009930:Organic Chemicals