About this Author
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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Monthly Archives

February 26, 2010

A Friday Book Recommendation

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Posted by Derek

This isn't exactly med-chem, but its focus probably overlaps with the interests of a number of readers around here. I recently came across a copy of A Field Guide to Bacteria and enjoyed it very much. I don't think there's another book quite like it available: it describes where you're likely to find different varieties of bacteria (from hot springs to your fridge), how they behave in a natural environment (as opposed to a culture dish) and how to identify them by field marks, if possible. It's not written for microbiologists, but it can provide a different perspective even if you work in the field (since many people that do focus on pathogens - really a very small subset of bacteria, when you get down to it).

I'm already inspired to set up some Winogradsky columns with my kids, perhaps with some unusual chemical additives to see what happens. If we discover anything, I'll report back. . .

Comments (11) + TrackBacks (0) | Category: Book Recommendations | General Scientific News | Infectious Diseases

HER2 Confusion

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Posted by Derek

For years now, drug companies and journalists have been touted the new era of personalized medicine. This is one of those things that always seems to be arriving, but is taking its time getting here. The industry has sunk a huge pile of money into biomarker research, and it's safe to say that it hasn't paid off yet - although, at the same time, one still has to think that it should, eventually.

Nature Biotechnology has a good article that shows how tricky the whole business can be. HER2 is one of the more validated cancer biomarkers, and there's a drug (Herceptin) that's targeted specifically for breast cancer patients that express it. So how's that going? Not so well:

A recent study from the University of California, San Francisco, reveals that one in five HER2 tests gives the wrong answer1. Furthermore, the article, which reviews the medical literature, reports that as many as two-thirds of breast cancer patients who should be tested for HER2 are not, and consequently a significant fraction of women treated with Genentech's Herceptin (trastuzumab) have never been tested for HER2 overexpression.

The health benefit provider Wellpoint, of Indianapolis, might dispute that finding. According to Genentech staff scientist Mark Sliwkowski, the insurer has data showing that 98% of its breast cancer patients are tested. However, doctors differ in their views on testing before prescribing Herceptin. “Some doctors don't know how to interpret test results, they prefer just to prescribe it and assess the patient's progress,” says Michael Liebman of the patient stratification company Strategic Medicine of Kennett Square, Pennsylvania.

More than a decade after the drug received US Food and Drug Administration (FDA) approval, the personalized medicine paradigm clearly has holes. . .

That it does. As the article goes on to explain, there are doubts about how good many of the existing HER2 tests are, worries about how they don't always agree, questions about whether some HER2-negative patients might be benefiting from Herceptin anyway, and more questions about those results due to uncertainties about the tests. That's the state of the art right there, folks, and it's clear that we have a long way to go. I don't see any reason why biomarkers (of various kinds, not just genetic) won't help us figure out which patients should be getting which drugs, but don't let anyone tell you that we're there yet.

Comments (15) + TrackBacks (0) | Category: Cancer | Clinical Trials | Regulatory Affairs

Layoff News

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Posted by Derek

More job loss news to report, unfortunately. Pharmalot comes in with an item that fits with what I'm hearing, that Sanofi-Aventis appears to be making small cuts, over and over, at its various sites. There hasn't been a single big announcement that I've heard, but the company seems to be shrinking headcount nonetheless.

And I've also heard recently that Astra-Zeneca is ready to announce more layoffs, although I don't have a handle on the size. This appears to be some of the follow-through from their earlier nonspecific announcements - it looks as if they're finally going to start getting down to some details. Anyone with more information on either of these situations is welcome to add it in the comments. . .

Comments (19) + TrackBacks (0) | Category: Business and Markets

February 25, 2010

Cranking Away

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Posted by Derek

Not as much time to blog this morning (and it's been hard getting into the site, since there are a lot of people who apparently want to know how to order some dioxygen difluoride). For one thing, I'm clearing a bunch of reactions out, and I've been devoting thought to how to do that in the laziest possible manner.

Maybe I should clarify that. What I mean is, how do I work up all these reactions quickly, in such a way as to make clean compounds that are worth testing, but spend the least amount of effort doing so? There are, of course, all sorts of brute-force ways to bang these things through, some of which would involve me not leaving my lab for the next three days or so, but I have other demands on my time. It's worth thinking about the most efficient way to do it.

Since these things I'm making all have acidic groups hanging off them, the most appealing idea I have right now is to use a basic resin to clean them up - as most med-chem types know, you can generally stick acidic compounds onto such resin, wash a lot of the crud off and throw that away, then bump your desired compounds off with some sort of acidic wash. This sort of solid-phase cleanup became popular in the combichem era, and has persisted for situations like this.

That's probably how I'll go, as opposed to, say, individually loading every single one of the compounds onto the HPLC machine. That would make me rather unpopular with the other people who might want to use that instrument before March is upon us, for one thing, and it would be complete overkill as well. These compounds are all pretty clean looking - a wash-and-rinse protocol should turn them out in good shape, and there's no need to use Super Ultimate Purification on them. (And besides, I'm making them all in reasonable quantity, which would bog down the HPLC even more).

An even more brainless way to do this workup would be to run every single compound through an automated column (like a Biotage). At least the HPLC has a liquid handler on it - I could set the thing up with a few rows of samples to inject, and walk away with some degree of confidence that it would run them. But the Biotage-type machines are usually one-at-a-time things, for larger samples. One batch of five grams of stuff would be perfect - two or three dozen at 100 mgs each, not so.

And all this makes me think of someone who used to work down the hall from me (no more clues than that!) I noticed that he was always cranking away in the lab, every time I went past. I mean, this guy looked like one of those multi-armed Hindu god statues, with each hand holding a round-bottom flask or a TLC plate. Impressive! Until I realized, after dealing with him a while, that the reason he was zipping around in there like a hamster was because he was doing everything in the most brutal and time-wasting way possible. He seemed to pick his reactions and protocols according to how much hand labor they involved: the more, the better.

I took a vow never to be him, and today I plan to live up to that. Measure twice, cut once and all that.

Comments (27) + TrackBacks (0) | Category: Life in the Drug Labs

February 24, 2010

Knocking on Doors

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Posted by Derek

A correspondent writes in with an interesting and useful question: he's with a small company that believes that it's discovered a useful lead compound in an area where they're hard to find. But no one there has any experience with knocking on the doors of Big Pharma to talk about a deal, and they're wondering about the best way to go about it.

I (and people like me) can provide some general advice. But I know that there are consultants out there who've brokered things like this before and have both contacts and expertise that can help out. But that just kicks the problem along: how does a fledgling company find one of those? Some startups naturally begin with connections of this sort,