So, as regular readers know, we have declared war on PAINS on the blog. As part of that effort, I (we?, not sure if Dan wants to be associated directly with it) introduced PAINS Shaming. Well, thanks to Angelo Pugliese and Duncan McArthur at the Beatson we have the latest paper to shame.
The nice thing is that they come right out and call it like it is: a Rhodanine. To reiterate, from the comment by Baell and Walters:
Rhodanines exemplify the extent of the problem. A literature search reveals 2,132 rhodanines reported as having biological activity in 410 papers, from some 290 organizations of which only 24 are commercial companies. The academic publications generally paint rhodanines as promising for therapeutic development. In a rare example of good practice, one of these publications (by the drug company Bristol-Myers Squibb) warns researchers that these types of compound undergo light-induced reactions that irreversibly modify proteins. It is hard to imagine how such a mechanism could be optimized to produce a drug or tool. Yet this paper is almost never cited by publications that assume that rhodanines are behaving in a drug-like manner.
And as predicted, this paper does not cite Voss et al. They cite dose-depedent responses for their compounds. Does it matter? Not to me. To their credit, they call these molecules tools, but also tout them for future therapeutic development. A PAIN can be a useful tool or even lead to non-PAIN containing compounds, but it requires a higher level of proof. I don't see that here.
So, here is your PAINS Shaming (Holiday themed):