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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« The NIH's Drug Repurposing Initiative: Will It Be a Waste? | Main | Drug Discovery on Radio 4 »

May 23, 2012

Another Vote Against Rhodanines

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Posted by Derek

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.

Comments (3) + TrackBacks (0) | Category: Drug Assays | Drug Development


COMMENTS

1. Pete on May 23, 2012 7:26 AM writes...

Here's one to check out for an example of assay results that looked OK but turned out to be otherwise:

dx.doi.org/10.1016/j.bmcl.2003.12.014

(Bioorg. Med. Chem. 2002, 10, 3197-3122)

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2. anchor on May 23, 2012 7:40 AM writes...

Derek: Call it some sort of dope addiction of scientists to rhodanine. We all realize that it is bad, but scientists will not be deterred using it again because it makes you and your results feel good!

Permalink to Comment

3. sgcox on May 28, 2012 11:41 AM writes...

Is this compound real ??

http://pubs.acs.org/doi/abs/10.1021/jm201442t

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