Update: the chemical probes portal mentioned here has since been updated and re-launched.
There’s a new paper on chemical probes out in Nature Chemical Biology, and right off, I have to disclose a conflict of interest. I’m a co-author, and I’m glad to be one. (Here’s a comment at Nature News, and here’s one at Science). The point of the article is that (1) many of the probe compounds that are used in the literature are inappropriate at best, and junk at worst, and (2) it’s time to clean up this situation.
How bad is it? Try these examples out:
. . .For instance, LY294002 was originally described in 1994 as a selective inhibitor of PI3 kinase and remains advertised as such by nearly all vendors. Yet by 2005, it was already clear that the compound inhibited many other proteins at the concentrations used to inhibit PI3 kinase. In the meantime, a large number of more selective and more well-characterized PI3 kinase inhibitors have become available.
The availability of these new inhibitors certainly obviated the need for LY294002 as a chemical probe, and it should be discarded as a selective research tool. Yet a search
of Google Scholar in 2014–2015 alone for ‘LY294002 and PI3 kinase’ returned ~1,100 documents.
And why not? You can still find people using staurosporine as a PKC inhibitor, even though it’s a kinase blunderbuss. Similarly, dorsomorphin is not a good choice to inhibit AMPK signaling, and chaetocin is a terrible excuse for a selective histone methyltransferase probe. I’ve written about others on this blog, as bad or worse.
But these things are all over the literature. People can’t keep up, or don’t, with the literature showing that these compounds (and many others) are problematic, and the suppliers keep selling them. Far too many researchers look something up in the catalog, see it listed as a “selective XYZ inhibitor”, and believe every word. Both the suppliers and the investigators are at fault, and the result is that the scientific literature ends up with garbage piles and oil slicks floating all over it.
Good probe compounds are not easy to find. Seeing one in somebody else’s paper places you at the mercy of their literature-searching skills if you don’t do some checking of your own. Ordering one up from a catalog proves nothing more than that company’s ability to sell it to you. To try to remedy this situation, this new paper also includes the launch of a web site, a wiki-based compendium of validated probes. The hope is that this will become a resource that everyone can turn to, a one-stop-shop that will save a lot of time, money, effort, and frustration.
It has only a few compounds in it as of this morning, but I plan to send in some suggestions of my own this week. (One of those is for a separate list of probes that are Not Recommended, so that people can find those as well). The plan is to put up editing functions soon so that people can do this themselves. I encourage people to send in feedback – this is an opportunity to try to fix a number of longstanding problems in the literature, and without something like this, these problems will only get worse.
Ideally, I’d like to see references to the site in the supplier catalogs, and attention paid to its listings by reviewers and authors alike. The excuses for using worthless chemical probes have never been good ones, and with any luck, there eventually won’t be any such excuses left at all.