Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice
Neelakantan H, Vance V, Wetzel MD, et al. (2018). Biochemical Pharmacology.
Summary
The study that put this class of compound on the map. The authors tested a series of small-molecule inhibitors of nicotinamide N-methyltransferase, an enzyme involved in cellular metabolism and energy balance, for their ability to cross membranes and act selectively against related enzymes. In cultured fat cells the inhibitors affected fat synthesis and the enzyme's reaction product. A potent inhibitor from the series was then tested in mice made obese by a high-fat diet, where the authors report reversal of the diet-induced obesity. Cell and mouse work aimed at validating the enzyme as a drug target.