I've updated the hit identification section of the Drug Discovery Resources. In particular I've added to the high-throughput screening analysis including more information on PAINS (Pan Assay Interference Compounds) first described by Baell et al DOI and subsequently summarised in an excellent Nature comment.

Academic researchers, drawn into drug discovery without appropriate guidance, are doing muddled science. When biologists identify a protein that contributes to disease, they hunt for chemical compounds that bind to the protein and affect its activity. A typical assay screens many thousands of chemicals. ‘Hits’ become tools for studying the disease, as well as starting points in the hunt for treatments.

These molecules — pan-assay interference compounds, or PAINS — have defined structures, covering several classes of compound. But biologists and inexperienced chemists rarely recognize them. Instead, such compounds are reported as having promising activity against a wide variety of proteins. Time and research money are consequently wasted in attempts to optimize the activity of these compounds. Chemists make multiple analogues of apparent hits hoping to improve the ‘fit’ between protein and compound. Meanwhile, true hits with real potential are neglected.

Also added a page on Aggregators. Promiscuous inhibition caused by small molecule aggregation is a major source of false positive results in high-throughput screening. To mitigate this, use of a nonionic detergent such as Triton X-100 or Tween-80 has been studied, which can disrupt aggregates, and is now common in screening campaigns DOI.