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Derek Lowe The 2002 Model

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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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« Science By Country | Main | Explaining It All »

May 8, 2008

Merck Bails on Natural Products

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Posted by Derek

Every few years, you hear talk of a renaissance in natural products-based drug discovery. Well, this news should postpone the next round of optimism for a bit longer: Merck is cutting their natural products program entirely. They've had a long history in that area, but no more. That C&E News item includes an interesting detail:

"The company disclosed that it would also be closing its 50-year-old natural products drug discovery operation based in Madrid after a Merck executive inadvertently included the plan in a PowerPoint presentation to an audience that included Merck employees."

Smooth move. I'm sure some interesting e-mails were exchanged around Rahway and Madrid after that one. When, when will we get the powerful regulatory oversight of PowerPoint technology that the masses have cried out for these many years?

The main thing I remember about Merck's operation in Madrid was when they made a big splash about ten years ago with a weird looking indole/quinone thing that directly activated the insulin receptor. It made the cover of Science and all sorts of press releases, and my biology colleagues starting pestering me immediately. "Hey, you chemists keep saying that there's no point in running a small-molecule screen against the insulin receptor!"

Well, as it turned out, we were right. I assured my co-workers on the next floor that the Merck compound was one of the least likely drug candidate structures I'd ever seen, and that I'd be intensely surprised if it went anywhere. In fact, I told them, seeing it on the cover of Science actually decreased the likelihood that it was anything useful. If Merck really had a small-molecule insulin mimetic, I reasoned, the program would be a real stealth bomber, for fear of sending all sorts of other companies into the same chemical space too quickly. This one had all the signs of the people involved saying "You know, the only thing this stuff is good for is getting on the cover of Science"

So it proved, eventually. The compounds never went anywhere. It looks like the most recent natural product-derived compound that Merck got onto the market was Cancidas (caspofungin), and that was seven years ago. Mevacor (lovastatin) will stand as the modern high-water mark of Merck's natural product work - presumably from now on.

Comments (21) + TrackBacks (0) | Category: Diabetes and Obesity | Drug Industry History


1. Still Scared of Dinosaurs on May 8, 2008 10:15 AM writes...

Looks like Spain might end up a little smaller on the patent-and-publication map.

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2. SRC on May 8, 2008 12:28 PM writes...

Derek, it's a bit shocking that your bio colleagues were too dull-witted to draw your conclusion regarding the Science cover.

"Hey, everybody, we've got a great lead in a new class of compounds addressing a huge market, but everyone hold off until we sew it up, OK?"

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3. Wavefunction on May 8, 2008 2:26 PM writes...

Looks like this was the group that published on the new antibiotics parnafungins (See JACS ASAP today)

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4. CMC guy on May 8, 2008 6:15 PM writes...

My impression is that Natural Products isolations as a area of interest is becoming less common in academia also. There are a few groups still performing this type work (mainly Japanese?) yet it often seems a more secondary than mainline focus (to synthesis or structural characterization). Unfortunate if is in decline as can be a valuable (& proven) tool in our belt for potential leads or drug molecules.

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5. Ed on May 9, 2008 1:52 AM writes...

Of the fifteen small molecule drugs approved in 2007, six were natural products or derivatives thereof (thats 40%!).

Who says the field is dead?

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6. burt on May 9, 2008 10:04 AM writes...

"I told them, seeing it on the cover of Science actually decreased the likelihood that it was anything useful"

Derek, you are smart guy, but this will end up as one of your most quotable lines. Definately "sad, but true".

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7. Cellbio on May 9, 2008 10:33 AM writes...

Ed notes a significant number of 07 NCEs were NPs or derivatives. These include azithromycin, topotecan and temsirolimus approvals for new indications. While these approvals represent significant advancments in clinical care, they don't light a fire for discovery folks thinking of novel approaches. Maybe there will be another rebirth as sytems biology intersects with NPs.

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8. LNT on May 9, 2008 10:59 AM writes...

What companies are left with NP research divisions?

Wyeth does (for now). Any more?

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9. Wavefunction on May 9, 2008 12:38 PM writes...

My take on natural-product based drugs us similar to that on extra-terrestrial intelligence. There's probably a lot of them out there, but how do you find them?

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10. processchemist on May 10, 2008 5:29 AM writes...

>What companies are left with NP research divisions?

a small one:

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11. bootsy on May 10, 2008 7:26 AM writes...

In reply to LNT (#8), Novartis also maintains an active natural products effort.

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12. Bob on May 10, 2008 11:44 AM writes...

In reply to LNT, there are lots of companies with NP divisions. Simply look up

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13. drug_hunter on May 11, 2008 6:32 AM writes...

I think natural products research will undergo a renaissance sometime in the coming decade. The challenge in natural products research IMHO is largely about separation and characterization, and as the technologies for those steps improves we will find novel compounds of different types than have historically been seen. Of course the synthesis of derivatives of natural products is challenging too, but in many cases is tractable, given sufficient diligence. I'm keeping a close watch on the field and my fingers crossed!

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14. befuddled on May 12, 2008 12:42 AM writes...

Does anyone know the status of platensimycin? Merck certainly made a lot of noise about that natural product a couple of years ago.

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15. sciwriter on May 12, 2008 10:04 AM writes...

I asked someone from Merck recently about platensimycin and their official word was that it is "still in early development." I find it hard to believe that its going anywhere quickly (or at all) given how long its been since they first hyped it.

Pfizer seems to have a pretty active natural products development program, at least in antibiotics.

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16. CMC guy on May 12, 2008 11:07 AM writes...

#12 Bob please clarify how to search the link you provide as I found no hits if I search "Natural Products". Perhaps you are suggesting genomics is a current form of NP research which is arguably true however in context here the interest is more "classically" rooted discovery programs. Based on limited feedback data so far there is not extensive emphasis in NP source of drugs apparently. #13 drug_hunter is perhaps correct although the screening/ID of active species is possibly more challenging then the technical aspects mentioned.

#9 Wavefunction many drugs can be traced back to folk medicines so does that represent past "visitations" in your analogy? Likelihood of finding drugs/aliens becomes even more extremely remote if we stop looking and just wait till we get contacted by a serendipitous agent/intelligent life.

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17. Bob on May 12, 2008 8:13 PM writes...

In reply to CMC guy, click on the sublink "biotechnology companies" in to find a long list of companies. Using the "product", "research", or "search" functions in these company links will reveal their activities in the field of natural products.

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18. ds on May 14, 2008 12:00 PM writes...

Does anyone know about companies (in either Europe or North America) that develop pharmaceutical products based on spices such as turmeric?

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20. Cesar Sanchez on June 1, 2008 2:52 PM writes...

I'm with drug_hunter (comment no. 13). A massive application of new high-throughput technologies (for sample analysis and processing, for genetic engineering of microbes and plants...) should yield the so-needed acceleration of drug discovery from natural products.

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21. Rakesh kumar Asthana on June 20, 2009 3:12 AM writes...

Natural Product research is a tedious job. It needs a hard working researcher with great patience to evaluate even minor amount of compounds isolated from natural products and their biological activity.Its structure ellucidation of complex molecule is a challenging job. China and US are in the race. Future of the natural product research is very pomising.

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