Pharma Blog Watch

A Look at Accidental Drug Discovery (In the Pipeline)
In his blog, Derek Lowe discusses recent reports of a lab mishap that led to the discovery of a new investigational cancer drug.

"The discovery (from the University of Rochester) has to do with PPAR-gamma compounds," he writes. "The PPARs are nuclear receptors, affecting gene transcription when small molecules bind to them." Researchers found that PPAR-gamma antagonists "had an unexpected toxic effect on some tumor cell lines. Their tubulin system was disrupted — that's a structural protein which is very important during cell division, and is the target for other known oncology drugs (like Taxol). The PPAR ligands seem to be messing with tubulin through a different route than anyone's seen before, though, and that definitely makes it worth following up on."

"But the tone of the press release is too optimistic. … It mentions 'high-dose' PPAR antagonist therapy as a possible cancer treatment, but take a look at the concentrations used: 10 to 100 micromolar. Even for cells in a dish, that's really hammering things down. And there's hardly any chance that you could attain these levels in a real-world situation, dosing a whole animal (or human). As blood levels go, those are huge."