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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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« The Supreme Court Makes Me Smile | Main | Nativis Update »

March 22, 2012

Shortage of Blogification

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Posted by Derek

No time to update today, unfortunately - a blizzard of Real Science (TM) is keeping things hopping, and my new laptop died on the train this morning during my usual blogging time.

So I'll use this chance to throw out a question: what topics haven't come up around here lately that we should be talking about? Blogfodder comes in around here pretty regularly, and I have a few topics in the queue, but I want to be sure not to miss out on interesting stuff. Thanks, and I'll see everyone tomorrow. . .

Comments (55) + TrackBacks (0) | Category: Blog Housekeeping


1. PPedroso on March 22, 2012 9:25 AM writes...

I would very much appreciate some general discussion about virtual screening present and future.

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2. Virgil on March 22, 2012 9:38 AM writes...

I would like some discussion of promiscuous targets...

We're always hearing about how drugs and other small molecules have off target effects. The story is very rarely presented from the other side. There are sets of proteins which appear to change in response to everything. No matter what you throw at the cell, these things just go up and down in response. MAP Kinases spring to mind, as does MnSOD in mitochondria - you just have to blink at the cells and these things will change. Same goes for various proteins that always show up as false positives in yeast-2-hybrid studies because they're just sticky. NF-KB is another one - it just responds to everything, regardless.

I'm not aware that anyone in the drug development field has reviewed this, or made a compendium for others to be wary of. What use are these proteins as potential targets?

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3. JAB on March 22, 2012 9:42 AM writes...

Amen on NF kappa B!

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4. Rick Wobbe on March 22, 2012 10:24 AM writes...

Yesterday's NYTimes article ( about how you can sue a manufacturer for damages if a branded drug causes harm, but you can not sue if the exact same drug does exactly the same thing but is a generic. Seems like a good example of how science, law, politics and business often look at the same thing and see it in vastly different ways and no one, except for perhaps some businesses, likes the outcome.

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5. JaosnP on March 22, 2012 10:25 AM writes...


I drove by the old Nativis building and don't see their name posted anymore. They either changed their name or are gone.

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6. Tony Zbaraschuk on March 22, 2012 10:34 AM writes...

More lab stories and Things I Won't Work With.

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7. DTM on March 22, 2012 10:42 AM writes...

Discussion about the career trajectory of industrial research scientists, and what viable changes in career path are open to those who are unfortunately laid off.

I've just graduated with a PhD in polymer chemistry and I'm working for a great small-sized biotech, but I wonder what my future holds 20 years down the line.

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8. Joe Loughry on March 22, 2012 10:58 AM writes...

Regarding Tony @ #6 lab stories and Things I Won't Work With, a cancer researcher friend once told me that she had no trouble at all handling toxins and viruses in her lab, but radioactives scared her. They get EVERYWHERE, she said, and she worked in constant fear of tracking it home.

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9. kissthechemist on March 22, 2012 11:04 AM writes...

I live for the "snake oil" posts. Remember the wine molecule guy? Priceless !!

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10. Pete on March 22, 2012 11:18 AM writes...

How justified are the common assumptions that we make in MedChem? To what extent is the practise of MedChem shaped by IP? Interfaces between disciplines in multi-disciplinary environments. What fundamental MedChem research should be getting done? What advice would you offer a young wannabe medicinal chemist before they start graduate school? What should we measure and what can we predict?

PPedroso, If you're interested in virtual screening, you might want to look at the current post in my blog in which I review a recent article on cooperativity and hot spots in the context of scoring functions.

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11. Pete on March 22, 2012 11:19 AM writes...

How justified are the common assumptions that we make in MedChem? To what extent is the practise of MedChem shaped by IP? Interfaces between disciplines in multi-disciplinary environments. What fundamental MedChem research should be getting done? What advice would you offer a young wannabe medicinal chemist before they start graduate school? What should we measure and what can we predict?

PPedroso, If you're interested in virtual screening, you might want to look at the current post in my blog in which I review a recent article on cooperativity and hot spots in the context of scoring functions.

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12. Triflate on March 22, 2012 11:24 AM writes...

@5: The Nativis website as well as their page on Linked are now devoid of all content, hmmm...

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13. Claire on March 22, 2012 11:50 AM writes...

@8 I don't think it's that radioactives spread more easily than other compounds, rather it's easy to track where they do get. If you have a colourless, odourless non-radioactive compound then you probably won't have a clue where it ends up as it's not easy to identify.

I did some work with para-nitro phenol and managed to dye half the lab yellow - even though I was being fairly careful. It's made me treat anything that's known to be nasty with respect.

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14. Cellbio on March 22, 2012 11:53 AM writes...

My current musings are about the industry struggles, and the role of scale in our failings. Certainly there are many factors, poor leadership, short horizons, low hanging fruit etc., but is a big part of the recent implosion a realization, driven with urgency with the capital market collapse, that the overall investment can't be supported by even by the most optimistic estimates of return. Do changes in the regulatory and reimbursement landscapes mean fewer companies can carve out earnings as later entrants, effectively terminating second tier companies?

Related to this, are Universities which are trying to fill dwindling grant dollars with innovation embarking on this flawed model of scale, giving up their great advantage of being opportunistic when the right thing comes along? Sat in a meeting this week where a revamping effort talked of improving ROI through more active efforts like patenting more, educating professors on commercialization and incubating companies, which at first I thought of as good, but now I wonder if it is a fool's pursuit, expecting multiples of prior success rates when commercially relevant innovation is at the least not scalable, and perhaps hindered by these efforts?

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15. Biotechtranslated on March 22, 2012 12:03 PM writes...


It would be interesting to hear your take on the "virtual biotech" model that seems to be in fashion once again (i.e. 3-5 people who develop a candidate purely through outsourcing).

I'm sure there are some interesting pros and cons with that model.


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16. Morten G on March 22, 2012 12:08 PM writes...

You promised a post on covalent drugs.

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17. Chrispy on March 22, 2012 12:11 PM writes...

I agree with Claire on radioactives being just easier to track, not particularly sticky. One graduate student lab I recall used a fluorescent dye which we were told was very toxic and to be very careful weighing, etc. Everyone thought they were careful until the black light came out at the end of the period and it was clearly everywhere. Once I worked on the synthesis of a compound which just happened to be very fluorescent and was able to observe the same phenomenon despite having a lot more experience and having only myself to blame. We all work in a dilute soup of what we touch!

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18. Student on March 22, 2012 12:12 PM writes...

I like what #7 mentioned. I'd like to see something about careers, areas to avoid, better ways to increase demand for the profession (ex. physicians do incredibly well lobbying), etc.

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19. PPedroso on March 22, 2012 12:14 PM writes...

Thanks Pete,

I will take a look. The problem is that blogspot is blocked at work. I will need to check it during my off time! :)

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20. MikeC on March 22, 2012 12:23 PM writes...

@14 That type of meeting might not have much of an impact on actually increasing revenues through patent licensing or other commercialization. On the other hand, wouldn't promoting the institution as a place where that stuff is happening (whether or not it actually is) help preserve its pieces of the public and corporate funding pies?

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21. patentgeek on March 22, 2012 12:29 PM writes...

Not in order of amusement:

1. Co-crystals in pharmaceutical development
2. More wine molecules and power of photons

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22. Anonymous on March 22, 2012 12:51 PM writes...

I've had this article on dichloroacetate show up in several not-so-private e-mails lately. I know you covered it once before, but it has apparently hit the conspiracy theory circle again.

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23. Cellbio on March 22, 2012 1:03 PM writes...

MikeC I think you have nailed one big goal of the effort, namely, entice more donors!

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24. Vader on March 22, 2012 1:07 PM writes...

In my opinion, you can't post too many "Things I Won't Work With" posts.

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25. road on March 22, 2012 1:24 PM writes...

@16 agreed -- covalent drugs

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26. MoMo on March 22, 2012 1:33 PM writes...

I always like discussing the Neurochemistry of Religion and Ceremonial Chemistry. How religions use cathedrals and large spaces to increase serotonin levels and the perception of grandiosity and greatness, others use rituals for the same effect, while some self-flagellate or bow repeatedly to change and augment submissive neurochemical behavior.

Seldom discussed online but so important in all cultures and lives. I'll be waiting!

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27. Mutant Dragon on March 22, 2012 1:33 PM writes...

I second the "virtual biotech" -- #15.

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28. LongLiveTheMBA on March 22, 2012 1:44 PM writes...

Pros and cons of grilled vs crispy chicken, especially as it applies to new pharma/biotech organizations. In other words, whether to be lean or to be mean.

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29. petros on March 22, 2012 1:49 PM writes...

Seumas Milne claimed in yesterday's Guardian

"In both the US and Britain it was the state, not big pharma, that funded most groundbreaking "new molecular entity" drugs, with the private sector then developing slight variations."

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30. John on March 22, 2012 2:01 PM writes...

How about prostaglandins and hair?

That would be the ultimate blockbuster, so it might be interesting to examine why there's relatively little ongoing investment in lifestyle drugs in general.

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31. Resveratrol Receptor on March 22, 2012 2:39 PM writes...

Druggable diseases that haven't been defined as diseases yet: (e.g. erectile dysfunction before Prophet Brindley)

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32. neo on March 22, 2012 3:31 PM writes...

Most discussions around the health of drug discovery have centered on productivity in increasingly crowded therapeutic areas, profits, and job losses. How about another perspective? If today was the day that the first human being contracted HIV, how long until we would have the pharmaceutical tools to turn AIDS from a death sentance into a chronic condition? Would we be faster now because we are smarter (LOL) and have better tools, or would it be slower because the industry has been eviscerated by job losses?

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33. Shazz on March 22, 2012 4:25 PM writes...

How about an exploration of the factors behind the recent shortfalls in manufacturing/distribution of several critical pharmaceuticals.

We in Australia in particular are at the end of a long supply chain and have been running short of basic things like penicillin and more exotic things like anti-mitotics for cancer patients recently (and I remember reading the USA ran out of the lethal injection drug too). Is this to become a more regular phenomenon in the future?

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34. RM on March 22, 2012 5:15 PM writes...

Joe Loughry@8 - Over the years I've developed a theory that most labs have at least one (but usually not many) compound/item that inspires fear and paranoid caution, while other items that might objectively be as dangerous have no such fear attached to them - and which item inspires fear varies between labs.

I think it's reflective of human psychology. People tend to get desensitized to possibly dangerous things they encounter frequently. The non-cynical interpretation is that they become familiar enough that the safety precautions used seem routine and not frightening. It's that one thing you use, but infrequently, that gets associated with paranoia. The safety procedures you need to use are different enough that they feel slightly clumsy, and don't signal "everything's as it should be, you're protected and safe", but rather reinforce "You're *this* close to disaster! Panic level up!".

I find it interesting to look at what a particular lab classes as its "concern number one" - and what other potential hazards they shrug off as routine business.

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35. chris on March 22, 2012 5:16 PM writes...

We often hear about the top ten drugs in terms of sales, I'd be interested in finding the top ten prescription drugs in terms of number of patients treated.

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36. cellbio on March 22, 2012 7:15 PM writes...

Chris, from disinfo dot com, referencing IMS Institute for Healthcare Informatics data:

1. Vicodin (hydrocodone/acetaminophen)
2. Zocor (simvastatin)
3. Lisinopril
4. Synthroid (levothyroxine sodium)
5. Norvasc (amlodipine besylate)
6. Prilosec (omeprazole)
7. Zithromax (azithromycin)
8. Amoxicillin
9. Metformin (Glucophage)
10. Hydrochlorothiazide

Interesting to reflect on for therapeutic area and site of target. 4 of ten in CV. I have thought that the productive nature of CV work, aided by the relevance of tissue baths recording vessel ring contraction, fueled pharma growth decades ago in the pre-target era.

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37. Cobalt on March 22, 2012 9:05 PM writes...

I'd be interested to hear you take on this article from Wired:

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38. MK on March 22, 2012 9:10 PM writes...

More on the model of outsourcing R&D, ever on the rise.

I guess the idea is to let the VCs take the early risk, and big pharma only buys later, when the technology/product is less risky. But VCs also prefer to wait until the research is fairly de-risked (I know this from experience). So... all of the early risky stuff falls to academics, funded by NIH? But NIH reviewers don't like clinically-relevant drug discovery projects; they say this work belong in industry (I know this from experience).

So how are the economics shaking out these days? I'd love to see a rough breakdown of how much money:
- big pharma spends on R&D, then and now (then = ?. The good old days?)
- VCs spend on preclinical activities, then and now
- NIH spends on drug discovery, then and now

Is preclinical drug discovery going to die?

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39. MK on March 22, 2012 9:17 PM writes...

Addendum to my post #38. NIH reviewers also detest high risk projects (even if potentially high reward). NIH may be the least innovative behemoth on the planet, thanks to peer review. With NIH now calling the shots on what early R&D gets funded, I think our chances of making breakthroughs are even worse than they were when big pharma MBAs were calling the shots.

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41. Rock on March 22, 2012 10:03 PM writes...

Some of the posts on radioactivity and poor chemical hygiene coupled with some recent high profile lab accidents got me thinking that a blog on the best ideas to improve laboratory safety could be very informative and might even save someone from harm.

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42. eugene on March 22, 2012 10:11 PM writes...

"I find it interesting to look at what a particular lab classes as its "concern number one" - and what other potential hazards they shrug off as routine business."

I'm really paranoid about OsO4, organomercury and organotin compounds I also don't like but not as much as the first two. I used to keep all of these far away in their own multiple containers and be really careful about weighing them out, spreading paper towels all over the place that would be thrown out after weighing, etc... Still didn't help me when someone was weighing out some reagent for a Stille coupling and left the pipette with about half a ml of the stuff just lying on my desk and slowly leaking its contents in the middle of my workbench while going to India for a one month vacation. It was right after I got that stuff on myself that I started getting these fainting spells (sometimes just from going up the stairs but initially for no reason), but it could be it's just because I'm getting older and I'm paranoid. Still, they've been getting less frequent two years on.

But other stuff that is dangerous I really don't care about. Like t-BuLi. Wear safety equipment and don't do stupid stuff. I used that stuff by the litre. Or KCN. Just put on gloves and labcoat and measure the stuff out by the grams, don't spill it and don't eat it and put the bottle back. Also, don't join the group no matter what you may hear about the fun times to be had doing total synthesis in Singapore. Easy.

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43. gippgig on March 22, 2012 10:48 PM writes...

This looks very relevant: A Map of the Human Toxome (

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44. g on March 22, 2012 11:55 PM writes...

How about some commentary on scientific deadends? Kinase inhibitors seemed like a fantastic idea, as well as gamma secretase inhibitors. There are hundreds of great ideas that have gone nowhere, but they are still good ideas.

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45. Chris on March 23, 2012 1:36 AM writes...

@36. cellbio

Brilliant. thanks.

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46. researchfella on March 23, 2012 2:43 AM writes...

@43: Do you think kinase inhibitors "seemed like a good idea" but have been a scientific deadend??? Check wikipedia or whatever for info on Gleevec, Tarceva, Sorafenib, Sunitinib, and many more. Some of these are blockbuster drugs.

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47. researchfella on March 23, 2012 2:51 AM writes...

How about a "where are they now?" review on these "40 drugs with buzz" decribed in 2006:

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48. kapow on March 23, 2012 6:04 AM writes...

I'd like to hear your take on the dial-a-molecule academic project going on over in the UK. How out-there is it in terms of a realistic goal?

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49. dick on March 23, 2012 11:08 AM writes...

All great ideas so far - should be a feast of new information in the coming months. Let me add one more topic: all that data accumulated over the last 40-50 years, locked away in warehouses in hand-written notebooks and probably going to be destroyed with each merger/downsizing/closure. Just the data on chemical reactions must be signifcantly bigger than what CAS/Reaxys offer - and it will all be lost...or will it?

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50. Anonymous on March 23, 2012 8:09 PM writes...

Please give us your take on covalent inhibitors...

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51. Anonymous on March 23, 2012 8:11 PM writes...

Cancer treatment vs diagnostic: a very interesting article in Wired:

What do you think?

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52. Anonymous on March 23, 2012 9:40 PM writes...

How about a state of the union address on Med. Chem. employment in the US. According to this article on breakout and considering all the med. chem. layoffs, we may be headed for a reversal. The question is when?

I just got back into the med. chem. game after a year on the street. I got lucky and a 25%+ increase in salary!! Again, I got lucky!

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53. Volphar on March 24, 2012 2:27 PM writes...

How about something on the real challenge to chemistry-as-we-know-it: sustainability.

Not of our jobs but rather the impact of vanishing catalytic metals, diminishing fossil-based raw materials, exponentially rising environmental legislation and public dissatisfaction, on the current practice of chemistry itself?

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54. davesnyd on March 25, 2012 7:09 AM writes...

How about getting Carnac the Magnificent to do some guest posting?

Specifically, I'd like to hear some medium (say, five year) and long (say, 10-20 year) predictions for the industry.

How (and by whom) will drug discovery be done in the future? Will it still be funded by private corporations? Will it be performed in the US and Europe? How will outsourcing affect it? Outshoring? Industrial and academic and non-profit collaborations?

How will large pharma, small and mid-sized pharma, CROs, academics and non-profits interact? How will the various tasks of the drug discovery/development/testing pipeline be performed and by whom?

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55. ann on March 26, 2012 5:04 PM writes...

#53: agreed. Sustainability would be a good topic - pharma is investing in green chemistry and has very ambitious goals, even of medicinal chemistry. See recent Pfizer and GSK publications in Green Chemistry on this topic. A better med chem route impacts safety (not handling nasty reagents!), cost of goods, time to transfer from med chem route to process route, etc...but people in med chem are usually under alot of pressure to generate results and the 'green' methods may require more work to sort out or be viewed as something which is just 'nice to have.'

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