Researchers pinpoint potent anti-obesity compounds

Obesity research has been a key area of interest for drug developers, and the gene FTO has recently shown promise as a potential target for new weight-loss drugs.

Mutations occurring in the FTO gene have been blamed as the strongest genetic determinant of obesity risk in people, but the mechanism behind this link has been unclear until recently.

Now, researchers from the National University of Singapore have identified several potent inhibitors that selectively target FTO, a gene that has been associated with fat mass and obesity in certain people.

Previous genomic studies have shown that people with certain variations of the FTO gene--including adults, children and people across various ethnic groups--are 70% more likely to become obese. The Singaporeans hope to target this large population with their new inhibitors, which are detailed in the journal Chemical Science.

Working with investigators from the Agency for Science, Technology and Research (A*STAR) and Nanyang Technological University, researchers used a drug discovery technique called dynamic combinatorial mass spectrometry.

Investigators pinpointed several FTO inhibitors, many of which are able to selectively target FTO over other proteins that are very similar structurally. The most potent one they discovered was 4-[N'-(4-benzyl-pyridine-3-carbonyl)-hydrazino]-4-oxo-but-2-enoic acid. The benefit of such selective inhibitors is that they significantly reduce the risk of unpleasant side effects since they are designed to seek out specific targets.

The researchers have filed a patent for the inhibitors through the National University of Singapore's Industry Liaison Office.

- get the study abstract
- read the press release

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