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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: Twitter: Dereklowe

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March 1, 2005

Too Interesting For Us

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Posted by Derek

How do we accumulate our piles of test compounds over here in the drug industry? Well, mostly, we make them ourselves. But we also buy collections of compounds. Some of them are from other companies that have gone under, and some of them are from outfits that do nothing but produce libraries of (putatively) interesting compounds. (You can buy some that they've already shared with other companies for a discount, or you can have a new one made up for you for a higher price.) That was a much hotter business ten years ago than it is now, but it's still going.

And we buy compounds from university labs. That's a little-known way (outside of chemistry, at any rate) that professors and their research groups earn some extra spending money. (Naturally enough, this practice also leads to some elbow-throwing between the research groups and the universities involved when each of them want a piece of the profits.) We generally pay a set price per compound, but you wouldn't want to buy every single thing that academia offers. Some of the stuff is quite interesting and useful, but many of the structures will become drug leads only when swine take to the skies.

I've helped evaluate lists of potential purchases before, and they're a mixed bag indeed. Once I looked over a collection from Leo Paquette's group at Ohio State. Now, he and his group did a lot of nice chemistry over the years, and there were a lot of useful compounds on the list. But there were also plenty of intermediates from his famous synthesis of dodecahedrane. Those represented a tremendous amount of effort from his students and post-docs, and were part of the history of organic synthesis.

And I didn't want us to buy them. For one thing, they didn't look much like drugs to me. "But what if they hit in our assays?" said one of my colleagues, trying to make the case that we should buy some. "That's what I'm worried about," I said. What indeed? If one of those structures turned out to be a wildly potent ligand for some protein target, what exactly were we going to be able to do about it? Follow the twenty-nine step synthesis to make more of it? No, in this case, I thought we were better off with nothing than with something we could never use. We passed.

Comments (1) + TrackBacks (0) | Category: Drug Assays


1. dan on March 2, 2005 9:05 AM writes...

A point too often not recognized or under-appreciated outside of the industry. It turns out to be relatively easy, in the wide world of biological and chemical space, to find something that hits your target. But the issue you mention is one of the main reasons for the marginalization of natural products, arguably one of the best sources of chemical novelty and diversity, in modern drug discovery. If the MadChemists can't play, ain't nobody gonna party.

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