Types is Types

Derek Lowe is my favorite drug blogger, and this latest is worth reading. You'll likely need a bit of The Wiki to get a bit of jargon, but again, it's worth it.

This new paper is going to annoy a lot of people, but I think that's fine. Its author, Arash Sadri, has undertaken an extensive review of the origins of all approved small-molecule drugs (1144 of them). His claim is that only 123 of them were discovered by purely target-based assay methods, and that the rest have to be described as discovered through phenotypic means. He notes that the share of target-based drugs in new approvals has grown over the years, but that there has never been a year when they surpassed the phenotypic ones.

In a nutshell: the Drug Industrial Complex has spent many Billions of dollars in an attempt to find a new and betterer way of finding drugs. Turns out, according to the paper, not so much. And, in fact, it doesn't surprise me; I've always been unconvinced that chemists, et al, have truly reliable methods to document and directly measure what happens at the atomic level.

Potency and selectivity for the stated target are simply not sufficient (by themselves) to make a drug, as anyone with any experience knows, but if we really believed in the "strong form" of the target-based drug discovery paradigm, wouldn't they be (outside of tox failures, of course).

Which is another way of saying, through the side door of course, that the Drug Industrial Complex's bleating that it costs billions and billions of Bongo Bucks to get a 'new' drug to patients; and therefore the Drug Industrial Complex needs yet more billions in profits to carry out its mission. That unit cost of success is driven up by the massive count of candidates that never make it through a 'good' PIII trial.

Sadri concludes that "even if target-based drug discovery recorded the effects of molecules on all proteins and every othersingle component of the human body, as in a hypothetical and impractically ideal polypharmacological target-based scheme, it would still have inferior efficiency compared tophenotypic drug discovery."

One has to constantly wonder whether keeping a compound 'in development' without regard to incremental results just to keep the flow of salaries going is really just confined to one-trick pony nano-caps?