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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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In the Pipeline

« Drugs and Money | Main | Commenting Issues »

February 1, 2008

A Few Questions For My Fellow Pharma Chemists

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Posted by Derek

1. You’ve got a compound repository, right? Lots of vials, robot retrieval systems if you’ve got the cash, all that stuff? What fraction of those vials are full of sticky stuff that are colored warning shades of dark orange, red, or soy-sauce brown? And of those, what fraction has had colorfulness overtake it while in your repository racks, as opposed to the stuff that arrived looking that way? Bonus question: are you aware of any cranberry-red wonder drugs, and have you ever heard of anyone formulating a big manufacturing batch for Phase III while checking to make sure it’s the right shade of brown?

2. You’ve got some molecular modelers, right? And you ask them to try to dock some of your compound ideas into your favorite binding sites? OK, first question: how many times have any of them come back to you saying that they can’t fit something in? If the answer is “never”, you have a problem with your modelers. Second question: if you do get told that your compound doesn’t seem to dock, do you keep going down the hall until you find someone who can jam your idea into the model? In that case, the problem is closer to home.

3. You’ve got biologists on your project, right? In vitro assay people, then the in vivo group, ready to test whatever makes it that far? So, how much compound do they ask for? And how much of that do they plan to actually use? When they ask, how much compound do you tell them you have on hand (or can make)? And what fraction of what you really have or can make is that, exactly? Depending on the ratio between these various answers, you can either have no problems or you can be living with quite a few different ones simultaneously.

Comments (3) + TrackBacks (0) | Category: Life in the Drug Labs


1. Moebius on February 1, 2008 2:02 PM writes...

Well, Rifamycins range from yellow to purple (with some red ones and blue ones). Making analogs of them, you get pretty cool looking TLC plates. And purifying is easy : just collect the colored stuff !

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2. weirdo on February 7, 2008 12:44 AM writes...

Not sure this isn't just disappearing into the ether, but:

1) About 5-8% are absolute crap. Of purchased molecules, about 25% came that way. Of internally prepared molecules, far less than 5%, I'd say. HOWEVER, about half of the internally prepared samples that have "gone off" should never have been submitted in the first place, no matter how pure they were -- for reasons you have posted on before!

2) Our modellers are pretty good at telling us molecules won't work. We tend to make a bunch of them anyway. Rather than consider this a "problem", however, I consider it very good practice. Negative data helps refine SAR too, and you're not pushing the boundaries if you only make molecules that you think SHOULD bind. (Yes, I know this sounds preachy, but it's a Sunday . . .). And I haven't worked on a project in years where making new analogues of the same core structures didn't eventually lead to a new, unpredicted binding mode.

3) At this point, we've trained our DISCOVERY biologists very well. They ask for what they actually need, plus 20% overage. We tend to tell them exactly how much we have, because we trust their judegement, and they understand the issues. It took about a year to get to this point, but that's where we are now. I note you didn't ask about toxicologists or formulations scientists though! Now THAT'S a whole 'nother ballgame! Never tell a toxicologist how many grams you think you can make!

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3. DANA on May 28, 2009 10:41 PM writes...

I was reading that the Red Bull Cola has been banned in Germany for containing cocaine or its matabolite benzoylecgonine. My problem is that I have been drinking it every day 2 to 4 cans per day for the last month. I have been drinking quite a bit because I have severe cluster headaches and the caffeine helps reduce the severity of the headache. Well I tested positive on a drug screen for cocaine and I know that is the only thing that would have caused it. I see that 1 can contain 0.13ug or 130ng per can and 0.4ug or 400ng per liter. Can you please help me find out who were the testing laboratory and a way of contacting them? I am a Police Officer and I’m also in the Military Reserves for 22 years, which I stand to loose every thing if I cannot prove that this beverage was the cause of my positive drug test. I do take benicar hct 40/25 and viagra but they don't cause positive results can u tell me if there is a way to calculate how much BE would be in a single 12 oz can given 1 can contains 130ng of cocaine. Was not given any test results guessing gc/ms was between 400-500ng. At least I was told 3 times he gc/ms cutoff. I also assisted narcotic officers 9 days before the test in which cocaine and crack were removed from the home, I was inside the home but I did not handle any of the drugs. But I did take two suspects to jail.

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