Lipinski's Anchor

Michael Shultz of Novartis is back with more thoughts on how we assign numbers to drug candidates. Previously, he's written about the mathematical wrongness of many of the favorite metrics (such as ligand efficiency), in a paper that stirred up plenty of comment. His new piece in ACS Medicinal Chemistry Letters is well worth a look, although I confess that (for me) it seemed to end just when it was getting started. But that's the limitation of a Viewpoint article for a subject with this much detail in it. Shultz makes some very good points by referring to Daniel Kahneman's Thinking, Fast and Slow, a book that's come up several times around here as well (in both posts and comments). The key concept here is called "attribute substitution", which is the mental process by which we take a complex situation, which we find mentally unworkable, and try to substitute some other scheme which we can deal with. We then convince ourselves, often quickly, silently, and without realizing that we're doing it, that we now have a handle on the situation, just because we now have something in our heads that is more understandable. That "Ah, now I get it" feeling is often a sign that you're making headway on some tough subject, but you can also get it when you're understanding something that doesn't help you with it at all. And I'd say that this is the take-home for this whole Viewpoint article, that we medicinal chemists are fooling ourselves when we use ligand efficiency and similar metric...
Source: In the Pipeline - Category: Chemists Tags: Drug Industry History Source Type: blogs