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February 1, 2008
A Few Questions For My Fellow Pharma Chemists
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.
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