I grew up on a wonderful little island called Jamestown (although technically it is Conanicut island and the town is Jamestown). It was a great place to grow up, especially because in the summer we lived walking distance to the beach. One of the very cool things about the beach is that it has an awesome sand bar that pokes up at low tide. That was the most fun part of the beach to me. One of the things we did was stand on the sand bar and dig our feet into it. You scrunch your toes into the sand until you hit something hard. Then you excavate with your toes around it. If you got a foot or so down (this took some patience) and got lucky you would find a quahog. Thems is good eating. Many an hour was spent doing this and bringing home dinner. Sometimes, you found something hard and started more excavation around it...and WHAM! Not a quahog, but a razor clam instead! There goes your day as blood starts gushing out of your foot stuck in a foot of mud. You can come up with a different approach to find the clam, but you still get hurt by razor clams. Eventually, you give up digging for clams with your feet because you hit one too many razor clams and you get your clams from Zeek's Creek Bait Shop.
We here at Practical Fragments have a great job, we get to pontificate on fragment papers. As most people know, its Good Cop (Dan)/Bad Cop (Me) by and large. It works for us and the blog gets read by more than our mothers. But this is an opinion blog, and as everyone knows (G-rated version): Opinions are like belly buttons, everyone has one. We welcome contrary opinions, sometimes even try to provoke them. Dan and I do very little coordinating for this blog beyond the "I will have something for Monday". So, when we both find something that bothers us, well that's worth discussion. One topic in particular Dan and I have found is PAINS (Pan Assay INterference Compounds).
PAINS are gaining traction as things to avoid in screening collections; there's even a Facebook page. The literature is pretty clear as to what these are and why they are bad. In my eyes, I am fine just removing them all from my screening deck and being done with them. In fragment space, there is MORE than enough other compounds that I don't worry about missing whatever chemical space they live in. However, as I have often said, a fragment is like pornography, the viewer knows it when they see it. As you may know, I am not one for hard and fast rules. If you want to keep PAINS-like compounds in your collection, fine by me. BUT, you must be aware that they are PAINS. You must know that they must be kept to a higher standard of evidence, you must do more controls, etc. And of course, if you are making tools then it doesn't matter if it is a PAIN (Dan and I disagree here.)
So, Practical Fragments gadfly Pete Kenny has a post up at his (recently renamed blog) about PAINS. In it, he takes Practical Fragments to the woodshed over PAINS, even though his main point is about how we make decisions on data. He starts his commentary by pointing to this post and calling it a "vapid rant". As noted in the comments to my post Pete immediately took exception to it believing the burden of proof should be on the blogger to demonstrate the guilt of the compound(s) in question. He also cites this post as one that should be wary of calling something crap or pollution. He then goes in to the ontogeny of PAINS and raises some points:
- PAINS study is irreproducible because structures and targets are not revealed
- Only 6 HTS campaigns were analyzed when 40+ were available
- All screens used Alpha-Screen, so this may not be very "PAN"
He then goes deep into the actual structure of rhodanines and how some are good, or less bad. I think Pete has lost the forest for the trees, or shrubs. Its not that there are probably some rhodanines that are NOT bad actors; but we know many are, and these require a higher level of confirmation than other compound classes. Not every clam you dig for is going to slice your foot open, but when enough do, but after enough do, you change your approach.