With increasing access to high throughput screening, academic drug discovery is being accompanied by a plethora of publications that report screening hits as good starting points for drug discovery or as useful tool compounds, whereas in many cases this is not so. These compounds may be protein-reactive but can also interfere in bioassays via a number of other means, many of which may remain unknown, and it can be very hard to prove early on that they represent false starts.1-4Publications arise only to mislead others. Examples of such compound cores are shown in Figure 1. If the reader of this abstract is working on any such compounds, he or she is strongly advised to desist from further progress: these compounds will only cause problems and will be highly unlikely to lead to anything useful. Wider awareness and recognition of these problematic compounds will help the academic drug-discovery community focus on and publish genuinely optimizable screening hits. This will be of widespread and general benefit. But are there occasions where a recognizable PAIN may actually be progressable? This presentation will delve into such issues.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. J. Med. Chem. 53 (2010) 2719-2740.2. Baell JB. Observations on Screening-Based Research and Some Concerning Trends in the Literature. Future Med. Chem. 2 (2010) 1529�1546.3. Baell JB. Redox active nuisance screening compounds and their classification. Drug Discov. Today 16 (2011) 840-841.4.Baell JB, Ferrins L, Falk H, Nikolakopoulos G. PAINS: Relevance to Tool Compound Discovery and Fragment-Based Screening. Aust. J. Chem. 66  (2013) 1483-1494.

PAINS: Are they always painful?

248th National Meeting (2014)

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