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May 8, 2008
Merck Bails on Natural Products
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 (18)
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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.
Permalink to Comment2. 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?"
Permalink to Comment3. 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)
Permalink to Comment4. 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.
Permalink to Comment5. 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?
Permalink to Comment6. 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".
Permalink to Comment7. 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.
Permalink to Comment8. LNT on May 9, 2008 10:59 AM writes...
What companies are left with NP research divisions?
Wyeth does (for now). Any more?
Permalink to Comment9. 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?
Permalink to Comment10. processchemist on May 10, 2008 5:29 AM writes...
>What companies are left with NP research divisions?
a small one: http://www.indena.com/pages/access.php
Permalink to Comment11. bootsy on May 10, 2008 7:26 AM writes...
In reply to LNT (#8), Novartis also maintains an active natural products effort.
Permalink to Comment12. Bob on May 10, 2008 11:44 AM writes...
In reply to LNT, there are lots of companies with NP divisions. Simply look up
Permalink to Commenthttp://www.genomicsdirectory.com
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!
Permalink to Comment14. 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.
Permalink to Comment15. 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.
Permalink to Comment16. 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.
Permalink to Comment17. Bob on May 12, 2008 8:13 PM writes...
In reply to CMC guy, click on the sublink "biotechnology companies" in www.genomicsdirectory.com 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.
Permalink to Comment18. 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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