Do you have what it takes to run a med-chem project? Take this simple test and find out:
1. You have a compound with a suspicious reading in a hERG assay, indicating possible cardiovascular trouble later on. Do you:
A) Brace yourself to scale up compound for dog cardiovascular tox (and brace the budget for paying for it), wondering if the animal group has gone through with that threat to switch to 60-kilo Irish wolfhounds.
B) Brace yourself to start your SAR over, most of the way back from scratch, because your compound doesn’t fit anyone’s hERG model (what are the odds that you could miss them all?) and you have no idea of what to fix first, or
C) Make a pest of yourself by pointing out all the historical compounds, now on the market and not causing trouble, that would have been dumped by running this same assay and taking it this seriously.
2. Your lead compound has come back positive in an Ames test. A re-test was negative. Do you:
A) Brace yourself to fight for your compound’s right to live, even though it will always have the Mark of the Beast on it for having failed that first Ames.
B) Brace yourself to start your SAR over, most of the way back from scratch, because there’s no such thing as an Ames-positive structural model anyway, and you have no idea of what to fix first (and no conviction that anything needs to be fixed at all, except that pesky Mark of the Beast business), or
C) Make a pest of yourself by pointing out that a good percentage of the things on sale at the supermarket wouldn’t pass an Ames test either, especially at your tox doses.
3. You have a compound that you need intravenous blood levels on, but it doesn’t want to dissolve in any of those namby-pamby iv vehicles. Do you:
A) Brace yourself for running the thing in the closest thing that looks like it might work, at the lowest concentration, even though it might not give you any data you can use (hey, at least you can say that you tried).
B) Brace yourself to start your SAR over, adding morpholines, methoxyethyls, all those solubilizing groups that make the structure say “I Used to be a Brick, And I Probably Still Am!”, even though you can’t think of a place to put them without killing your activity, or
C) Make a pest of yourself by arguing for some weirdo vehicle that you pulled out of the literature (Dr. Pepper, hair gel, balsamic vinegar, etc.), which your PK people have never heard of and would rather shave their heads than take the time to validate.