PAINS or Pan Assay Interference Compounds, are a class of compounds that commonly show up in high throughput screens (HTS) for small molecule inhibitors (you can read more about them here , here and here).
When asked why in his opinion this paper made such an impact, Baell gave an interesting answer: basically it really hit a nerve, and the timing was just right. According to Baell, their group lead some of the first academic HTS efforts, and stumbled upon these PAINS molecules again and again. By the time the paper was published, there were probably dozens of academic labs performing screens and it really resonated with them. Another possible reason for the wide acceptance of this work might have been ex-pharma people, turned academics, who knew these molecules from their past but could not talk about them. Baell mentions for instance that for Chris Lipinski “it was a breath of fresh air…”.
From a practical stand-point you can use this server from the Oprea group to filter your molecules and avoid future PAINS.