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April 10, 2013
Pharmacology Versus Biology
There's a comment made by CellBio to the recent post on phenotypic screening that I wanted to highlight I think it's an important point:
In drug discovery, we need fewer biologists dedicated to their biology, and more pharmacologists dedicated to testing the value of compounds.
He's not the first one to bemoan the decline of classic pharmacology. What we're talking about are the different answers to the (apparently) simple question, "What does this compound do?" The answer you're most likely to hear is something like "It's a such-and-such nanomolar Whateverase IV inhibitor". But the question could also be answered by saying what the compound does in cells, or in whole animals. It rarely is, though. We're so wedded to mechanisms and targets that we organize our thinking that way, and not always to our benefit.
In the case of the compound above, its cell activity may well be a consequence of its activity against Whateverase IV. If you have some idea of that protein's place in cellular processes, you might be fairly confident. But you can't really be sure about it. Do you have enzyme assays counterscreening against Whateverases I through V? How about the other enzymes with similar active sites? What, exactly, do all those things do in the cell if you are hitting them? Most of the time - all of the time, to be honest - we don't know the answers in enough detail.
So when people ask "What's this compound do?", what they really asking, most of the time, is "What does it do against the target that it was made for?" A better question would be "What does it do against everything it's been tested against?" But the most relevant questions for drug discovery are "What does it do to cells - and to animals? Or to humans?"
Update: Wavefunction, in the comments, mentions this famous article on the subject, which I was thinking of in the first paragraph after the quote above, but couldn't put my finger on. Thanks!
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