Mimicking Gastric Bypass-Updated

What if you could get the metabolic benefits of gastric bypass surgery, without actually having the surgery?
No, this isn’t a sketchy infomercial. It’s honest-to-goodness medicinal chemistry research. This week in C&EN, Aaron Rowe has the skinny on research toward understanding the gut.

As he explains, people who undergo gastric bypass surgery don’t just lose weight, but many times recover from type 2 diabetes to boot. “For medicinal chemists seeking treatments for metabolic disease, this phenomenon provides a tantalizing avenue for developing diabetes drugs that target the gastrointestinal tract,” he writes. The key seems to be understanding how the surgery affects chemical signaling in the intestine, perhaps adjusting overall metabolism so it reaches a healthier, non-diabetic state. At the ACS Meeting in San Francisco, scientists told him and other conference attendees about a few of the big players in that signaling jamboree:

-Bile acids

-Fatty acid amides

-Triglycerides

Rowe then describes examples of drug candidates those scientists are working on that appear to affect signaling in each of those areas. Some of the experimental drugs are in early-stage clinical trials.

UPDATE 4/20: For example, fatty acid amides are agonists of a G-protein-coupled receptor known as GPR119, so companies are interested in mimicking that effect with a synthetic GPR119 agonist. “It is truly amazing how many companies are pursuing GPR119 as a target,” Rowe tells me. In the article, he mentions Arena Pharmaceuticals’ two generations of GPR119 agonists. The compounds are JNJ-28630355 and APD597, the latter of which is in Phase I clinical trials. GlaxoSmithKline’s GSK1292263 is currently in Phase I clinical trials.

Selected other firms who’ve done research in the GPR119 area:
OSI Pharmaceuticals
Schering-Plough

The above list is lists are by no means comprehensive, of course, and researchers still have plenty to learn about the biochemistry that happens in the aftermath of surgery. But this article got me thinking about how many times we’ve truly tried to mimic the effects of a surgery with a pill. It seems to me that a lot of the drugs that we have are meant to either do better than what surgery can accomplish (ie lobotomy) or complement a surgery (some chemotherapeutics).

Author: Carmen Drahl

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