Zafgen’s ZGN-433 shows promise for obesity- so what’s it look like?
Jan05

Zafgen’s ZGN-433 shows promise for obesity- so what’s it look like?

Just in time to coincide with January's massive uptick in gym-going, Cambridge, MA startup Zafgen has announced good news about its experimental weight-loss drug for severe obesity. The molecule, ZGN-433, helped a small group of severely obese women (with body mass index of 32-45) lose weight- more so than a placebo. Weight losses varied from person to person, but the midpoints of the range of weight loss results were attention-getting: weight loss of 1 kilogram (2.2 pounds) per week, and 3.1 percent of body weight after 26 days, when the trial concluded. Women taking ZGN-433 in the 24-person study also experienced meaningful changes to their triglyceride levels and levels of LDL cholesterol, the so-called "bad cholesterol". The news spurred coverage at FierceBiotech, Xconomy, and many other news outlets. It's too early to tell whether ZGN-433 will become an FDA-approved weight loss drug. But it's encouraging to see companies still plugging away at the obesity problem even in light of the challenging year obesity drugs had in 2010. And Zafgen's announcement today contains some additional tidbits that point interested medicinal chemists toward the kinds of structures Zafgen might be working on. When we last covered Zafgen, the company had revealed the target of its experimental drugs, methionine aminopeptidase 2. And we learned that in animal studies, Zafgen was using a naturally-occurring molecule as a methionine aminopeptidase 2 blocker- fumagillin, or ZGN-201 in the company's parlance. We knew Zafgen was using another molecule in human trials (that's ZGN-433), but at the time the company didn't disclose the molecule's structure, or the name of the company they licensed the molecule from. In today's announcement, Zafgen unveiled that company's name: ZGN-433 was initially developed at Korea's Chong Kun Dang (CKD) Pharmaceuticals. So I decided to perform a Google Patents search to see what kind of structures CKD has patented. My very cursory search revealed four patents but as you can see below, some of the sample structures in the patents differ quite a bit from fumagillin. Zafgen's president and CEO Thomas Hughes told us that fumagillin's long double bond rich tail is troublesome, and it looks like it's gone in both these possibilities. Images: Zafgen and U.S. Patent Office UPDATED: corrected image...

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