Dan and I teach a short course on FBDD; next chance to catch a version in October. My favorite part of Dan's section is when he goes off on PAINS and the continuing pollution of the literature. Rhodanines in particular get Dan's dander up. I often come off as anti-academic because many of their "drug discovery" papers are crap. Or they claim something is a lead without it being one. I think it is time to start PAINS shaming these papers. For those of you not intimately familiar with "shaming" it is very popular with dog shaming. Well, here is our first PAINS Shaming. This paper (pointed out by Matt Netherton at B-I, thanks Matt!) unabashedly points out the offensive molecule as a rhodanine. In the article, they point out:
What is particularly interesting about the most active species investigated here is that it has a structure that is very similar to that found in the drug epalrestat, an aldolase reductase inhibitor that is used to treat diabetic neuropathy, and is approved for clinical use in Japan, China, and India. This is encouraging because rhodanines as a class are known to often have activity in widely different assays, and indeed computer programs such as PAINS categorize, [our compounds] (as well as epalrestat) as possible “pan assayinterference compounds”. This can mean that the compounds cause false positives in assays, or that they may be multitarget inhibitors. In some cases multitargeting may be undesirable; however, in the context of anti-infective development, multitargeting is expected to increase efficacy as well as decrease the possibility of resistance development, both very desirable features.
I am sorry, but this is exactly the Underpants Gnomes business plan. All I can say after reading this is who's reviewing this crap and saying it is all right?