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July 15, 2008
Metabolic Hope Springs Eternal
Now, if I were still doing metabolic disease work, I'd be all over this target: CAMKK2, which is mercifully short for "Ca2+/calmodulin-dependent protein kinase kinase 2". (Kinase nomenclature has been out of hand for years, in case you're wondering).
CAMKK2 is right in the middle of a lot of pathways that are known to be important for regulation of appetite and glucose levels, namely ghrelin, AMPK, and NPY. These have been rather hard to approach directly with small molecules, or (in the case of NPY) hitting them hasn't been enough by itself. That's the problem with a lot of potential therapies for obesity, as I've mentioned here before. As a behavior, eating is full of overlapping backup redundant pathways, since we're all descendants of creatures that ate whatever they could, whenever they could. The ones whose feeding could be easily shut down or interrupted didn't make it this far.
So even though the field is littered with things that haven't worked out, perhaps a target like this, which seems to be more upstream, might have a better chance of success. We're definitely going to find out. Given the number of companies interested in this area, and the number with kinase expertise, someone's going to be able to take a good swing at this one. The benefits might go beyond weight loss - animals given a known inhibitor (STO-609, a Sumitomo compound) were also resistant to the bad effects of a high-fat diet, putting on less weight than controls and showing better glucose control.
Of course, the fact that Sumitomo had a compound years ago that hits this target so well makes you wonder what ever happened to it. I can't find much about why it didn't progress, but you can be sure that other people are asking that same question right now. . .Update: see this comment for more on this topic. . .
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