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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

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June 23, 2005

News Flash: I May Not Be a Fool

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Posted by Derek

I now have my experimental results, at long last. And, well, I have to say that I seem to have something.

This batch was set up with fifteen different chemical structures, and I was looking for the same effect in each run. For each structure, there was an experiment that should have shown the effect I'm after, producing a new product, then a control (without a key ingredient) which should have shown little or nothing, and another control (with the key ingredient present, but with another compound added that should have blocked it from doing anything.)

I thought at first that I had fallen completely on my face, because as I looked over the first five or ten structures, I saw the same discouraging pattern. Next to nothing in the blank control runs, which was fine. But the numbers from the corresponding key-ingredient experiments were identically low, which was the inescapable sign of nothing going on. I'd also seen some where the experimental run showed something, but the corresponding blank showed the same exact levels - again showing that my experimental conditions weren't changing anything, but that I just had a high background rate of reaction.

I was using strong language by the time I got to number twelve, which showed a pretty high value in the experimental run. I looked over to the blank run, expecting to see the same levels, another high-background dud - but it really was a blank this time. Almost nothing there. The experimental run was at least fifty times higher. I held my breath as I looked at the second "inactivating control" run, and there it was -it went right back to the blank value, as it should if my hypothesis was correct. I had set up all the experiments in duplicate, and this morning I got the repeat data, which matched the first set very tightly. It appears to be real.

And to go along with this, these experiments also included the best candidate from my first attempts, the one that got me excited about running these follow-ups in the first place. It had made a lot of product again, although just three or four times the high background rate in the blank reaction, as it had been before. But had the inactivating control experiment knocked it back down to those values anyway? It had.

And both that one and the new winner are structurally quite similar, and they're the only two of that exact class that I've run. It's becoming increasingly clear to me that I finally have something that works, after three years of on-and-off attempts. I hardly know what to do with myself.

Well, that's not quite true. I have another variation ready to go, with ten or fifteen new structures of a different type, and I have time to incorporate what I've learned from this run before they go off. It's time to see just how far this stuff can be pushed.

Comments (8) + TrackBacks (0) | Category: Birth of an Idea


COMMENTS

1. Richard on June 23, 2005 11:17 PM writes...

congratulations that sounds exciting. The patience required for your line of work is extraordinary.

Permalink to Comment

2. Sam Jaffe on June 24, 2005 9:19 AM writes...

Conratulations Derek! Although I have no idea what you're working on, I feel like I'm part of the lab, having read your posts for more than a year now. Now show me what it does in mice!

Permalink to Comment

3. Mark on June 24, 2005 10:38 AM writes...

Fantastic!

Reminds me of very similar moments I've had very early in the morning in the NMR room during grad school....the waiting, hoping and clenched teeth patience through instrument foibles seemingly placed there by above to make the moment of long-awaited, undisputed victory that much sweeter.

I have to admit I am dying to know what sort of transformation this is...maybe some heretofore unknown C-C bond forming reaction that uses a cheap, air and water tolerant transition metal in lieu of the usual Pd, etc....and now the suspense till you let us all in on it!

Permalink to Comment

4. otey on June 24, 2005 11:50 AM writes...

I've been following your experiment for a year or so. I have no idea what the chemistry is all about. I wouldn't understand it if you tried to explain it, but I am very happy for you.


The magic of blogs.

Permalink to Comment

5. The Novice Chemist on June 24, 2005 2:05 PM writes...


Ya know, Mark, I wasn't convinced that this was chemistry. I thought it might be some sort of biology project. But I'm pretty sure that Derek's working on some new heterocyclic chemistry (isn't that all of med chem, pretty much?)

Permalink to Comment

6. schinderhannes on June 27, 2005 10:33 AM writes...

Congradulations to you!
That sounds like your up to something real, possibly something big......

I hope the least you get out of this is a nice publication!

TTFN
Hannes

Permalink to Comment

7. pyrokinetics on June 27, 2005 4:41 PM writes...

Derek, I realize you may not be able to say much more about your experiment but clearly your audience has been following these posts for a while. Can you elaborate *vaguely* whether your experiment is a pure research pie in the sky thing or whether it's more of a I've discovered a new reaction that will allow me to develop innovative drugs?

Permalink to Comment

8. Derek Lowe on June 27, 2005 5:44 PM writes...

That's a very fair question to ask, and the answer is "both." It's a blue-sky type research project, of the kind that we don't do very much of, but it's related to a potential new method for drug discovery.


If it weren't, I wouldn't feel as if I could ask other groups at my company to help me out, as I have on several occasions.

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