Years Worth of the Stuff

This time last year I mentioned a particularly disturbing-looking compound, sold commercially as a so-called "selective inhibitor" of two deubiquitinase enzymes. Now, I have a fairly open mind about chemical structures, but that thing is horrible, and if it's really selective for just those two proteins, then I'm off to truck-driving school just like Mom always wanted. Here's an enlightening look through the literature at this whole class of compound, which has appeared again and again. The trail seems to go back to this 2001 paper in Biochemistry. By 2003, you see similar motifs showing up as putative anticancer agents in cell assays, and in 2006 the scaffold above makes its appearance in all its terrible glory. The problem is, as Jonathan Baell points out in that HTSpains.com post, that this series has apparently never really had a proper look at its SAR, or at its selectivity. It wanders through a series of publications full of on-again off-again cellular readouts, with a few tenuous conclusions drawn about its structure - and those are discarded or forgotten by the time the next paper comes around. As Baell puts it: The dispiriting thing is that with or without critical analysis, this compound is almost certainly likely to end up with vendors as a “useful tool”, as they all do. Further, there will be dozens if not hundreds of papers out there where entirely analogous critical analyses of paper trails are possible. The bottom line: people still don’t realize how ...
Source: In the Pipeline - Category: Chemists Tags: The Scientific Literature Source Type: blogs