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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 Horse Latitudes | Main | Nobel Update: RNAi Wins »

October 1, 2006

Test Your Skills!

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Posted by Derek

Are you qualified to be a medicinal chemist? Take this simple quiz!

1. You synthesize a new drug candidate. It won't even dissolve in hot DMSO. Do you. . .
(a) Chuck it into the chemical waste, because it's never going to be a drug
(b) Wonder if it's clean, because you're never going to be able to get it down the LC/MS
(c) Send it in for the assays, because you never know.

2. You've just received the results of a crucial in vivo test of your project's best candidate. It was exactly as active as powdered drink mix. Do you. . .
(a) Blame the animal group for fouling up the dosing
(b) Blame the PK group for fouling up the results
(c) Feel a sense of relief that maybe there's an assay that you might have managed to finally kill

3. Your compound kills mice. But it makes rats fat and happy. Do you. . .
(a) Feel a sense of relief that at least your main tox species is still in the running
(b) Close your eyes, hold your breath, and scale up for the dog
(c) Wonder what it would do to Kevin Trudeau?

4. You need to make a competitor's compound, but their patent synthesis just doesn't work. Do you. . .
(a) Stare out the window, muttering things about disclosure of best mode
(b) Set up a literature alert, hoping for a process patent application to clear things up
(c) Rub your hands together and send the synthesis out to a contract lab, turning it into their problem?

5. Your lab has been assigned a yearly minimum number of analogs for performance review. Do you. . .
(a) Tell your group to send in every intermedidate compound, even the smelly unstable brown ones
(b) Feel a sense of relief that at least they're not asking for a quota of active compounds
(c) Reach for the big bottle of DCC, 'cause if it's amides they want, it's amides they'll get

Comments (11) + TrackBacks (0) | Category: Life in the Drug Labs


COMMENTS

1. Kay on October 2, 2006 5:29 AM writes...

(d) Dream up another set of 'rules' that don't work, then sit back and bask in the glow.

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2. milkshake on October 2, 2006 9:52 AM writes...

Hey, the parody is not funny! Your quiz reminded me exactly why I left the pharma industry.

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3. LNT on October 2, 2006 12:24 PM writes...

We really should start up a series of posts entitled "You know you're a medicinal chemist when..."

I'll start:
You know you're a medicinal chemist when you trust your molecular modeler's opinions about as little as you trust the latest bad results from your in-vivo pharmacologist.

You know you're a medicinal chemist when you haven't seriously scanned an issue of JACS in over 5 years.

You know you're a medicinal chemist when you have had to resynthesize at least 5 compounds in order to get acceptable CHN/HPLC analysis for your submission to J.Med.Chem.

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4. milkshake on October 2, 2006 1:09 PM writes...

You know you are a medicinal chemist when you stop writing yields at the end of experimentals. When you prefer prep-HPLC over crystalization. When you begin to avoid chiral centers (which you cannot buy as building blocks). When you stop using NMRs and go through all steps on LCMS alone. When you get excited about making a heterocycle with 2 rings and 3 nitrogens by cyclization that uses hot methanesulfonic acid as a solvent. When all axperiments are run either in microwave or at RT overnight. When you begin to think that "silyl" is nickname for dim manager.
When you start hiding half of your synthesized material from biologists and management alike. When you forget what solvent still is used for. When you buy your LDA from ALdrich. When you start thinking how to bust your own patents. When you write the first faked patent experimental procedure.

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5. Chemist of Sorts on October 2, 2006 1:36 PM writes...

The LDA comment reminds me of a consulting session I did a few years back with Andy Myers when I was an associate. I asked him if using Aldrich LDA made a difference from making it yourself. He simply shook his head and muttered "kids these days".

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6. milkshake on October 2, 2006 1:47 PM writes...

Andy Myers is a genuinely fine and considerate man - a rarity among the big-ego guys from the first league. I knew him only briefly - he just moved over and was starting his group there - but I would work for him any time.

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7. syn on October 2, 2006 2:55 PM writes...

Some of the questions I have multiple answers to, and in some of the others I can't think of a better thing to do than terminate the project. Sad situation being a medchemist.

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8. Milo on October 3, 2006 11:21 AM writes...

So... was being a med chemist always this depressing?

Derek (or any one else who is older than me...;-), was the industry as frustrating as it now seems to be when you joined it?

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9. Derek Lowe on October 3, 2006 1:19 PM writes...

Ah, it's always been this way, as far as I can tell. But it's not as depressing as I seem to have made it sound. This needs a follow-up post, which I'll start in on.

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10. skatesailor on October 3, 2006 11:33 PM writes...

In re Milo at 11:21 am on Oct. 3rd.

No, the industry was not always this depressing, but often was more depressing when I joined it in 1973. Then and later, some biologists did not bother to test submitted compounds, did not report what they found, or screwed up an assay of their own devising. In one notorious case in which we sought certain antagonists, the responsible biologist unwittingly but irresponsibly allowed the sensitive agonist to be degraded, so compromising the project. As the outcome, we discovered antagonists of unknown relevance. In another case, our immunologist retested the lead compound in each assay of newly synthesized analogs, testing the lead at three doses of about 0.3, 3, and 30 mpk. The measurement errors were so large that none of the three doses was distinct from any other. That no dose-response effect existed suggested that no measurable immunological phenonmenon was occurring, which squandered the efforts of about ten chemists working nearly 2 years. Provoked by the lack of improvement, one of the chemists plotted all the immunologist's non-results with the lead compound, and so discovered the debacle, finding that the lack of a dose-response effect was reproducible.

Efforts to discover drugs remind me of H. L. Mencken's view of extra-marital sex. The Sage of Baltimore said, "Adultery is time-consuming, expensive, and likely to be humiliating."

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11. Stu Savory on October 5, 2006 1:34 PM writes...

"You know you're a medicinal chemist when..."

You take a deep breath of Tellurium just to get a month off work (in quarantine) ;-)

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