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November 29, 2012
Another drug repurposing initiative is underway, this one between Roche and the Broad Institute. The company is providing 300 failed clinical candidates to be run through new assays, in the hopes of finding a use for them.
I hope something falls out of this, because any such compounds will naturally have a substantial edge in further development. They should all have been through toxicity testing, they've had some formulations work done on them, a decent scale-up route has been identified, and so on. And many of these candidates fell out in Phase II, so they've even been in human pharmacokinetics.
On the other hand (there's always another hand), you could also say that this is just another set of 300 plausible-looking compounds, and what does a 300-compound screening set get you? The counterargument to this is that these structures have not only been shown to have good absorption and distribution properties (no small thing!), they've also been shown to bind well to at least one target, which means that they may well be capable of binding well to other similar motifs in other active sites. But the counterargument to that is that now you've removed some of those advantages in the paragraph above, because any hits will now come with selectivity worries, since they come with guaranteed activity against something else.
This means that the best case for any repurposed compound is for its original target to be good for something unanticipated. So that Roche collection of compounds might also be thought of as a collection of failed targets, although I doubt if there are a full 300 of those in there. Short of that, every repurposing attempt is going to come with its own issues. It's not that I think these shouldn't be tried - why not, as long as it doesn't cost too much - but things could quickly get more complicated than they might have seemed. And that's a feeling that any drug discovery researcher will recognize like an old, er, friend.
For more on the trickiness of drug repurposing, see John LaMattina here and here. And the points he raises get to the "as long as it doesn't cost too much" line in the last paragraph. There's opportunity cost involved here, too, of course. When the Broad Institute (or Stanford, or the NIH) screens old pharma candidates for new uses, they're doing what a drug company might do itself, and therefore possibly taking away from work that only they could be doing instead. Now, I think that the Broad (for example) already has a large panel of interesting screens set up, so running the Roche compounds through them couldn't hurt, and might not take that much more time or effort. So why not? But trying to push repurposing too far could end up giving us the worst of both worlds. . .
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