Practical Fragments has previously noted that many pan-assay interference compounds (PAINS) can be found in nature. Indeed, they’ve also found their way – unintentionally – into journals published by Nature Publishing Group. In an effort to educate the scientific community about these artifacts, Jonathan Baell (Monash University) and Mike Walters (University of Minnesota) have just published a Comment in Nature entitled “Chemical con artists foil drug discovery”. This is the clearest discussion I’ve yet seen of PAINS, and it deserves to be widely read.
Since the article is open-access I won’t go into depth here, other than to say that the researchers propose three steps to avoid PAINS.
1) Learn disreputable structures.
As a start, the paper provides a rogue’s gallery of some of the worst molecules, along with memorable interpretations by award-winning New Yorker cartoonist Roz Chast. It would be nice to see this posted in every academic screening center.
2) Check the literature.
This is even easier than having to learn structures, and should prevent people from embarrassing themselves by publishing research that is obviously flawed.
3) Assess assays.
Multiple orthogonal assays are useful for all science, not just FBLD!
Together with the recent C&ENstory and ACS symposium, this article ensures that PAINS are finally reaching the level of recognition such that scientists, reviewers, and editors will no longer be able to claim ignorance. Willful negligence may be another matter, but at least people will be able to recognize it as such.