For those of you who'd had to explain to colleagues (in biology or chemistry) why you're not enthusiastic about the rhodanine compounds that came out of your high-throughput screening effort, there's now another paper to point them to.

The biological activity of compounds possessing a rhodanine moiety should be considered very critically despite the convincing data obtained in biological assays. In addition to the lack of selectivity, unusual structure–activity relationship profiles and safety and specificity problems mean that rhodanines are generally not optimizable.

That's well put, I think, although this has been a subject of debate. I would apply the same language to the other "PAINS" mentioned in the Baell and Holloway paper, which brought together a number of motifs that have set off alarm bells over the years. These structures are guilty until proven innocent. If you have a high-value target and feel that it's worth the time and trouble to prove them so, that may well be the right decision. But if you have something else to advance, you're better off doing so. As I've said here before, ars longa, pecunia brevis.