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  • Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.

Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.

Biochemical pharmacology (2017-11-21)
Harshini Neelakantan, Virginia Vance, Michael D Wetzel, Hua-Yu Leo Wang, Stanton F McHardy, Celeste C Finnerty, Jonathan D Hommel, Stanley J Watowich
RÉSUMÉ

There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors. Membrane permeability of NNMT inhibitors was characterized using parallel artificial membrane permeability and Caco-2 cell assays. Selectivity was tested against structurally-related methyltransferases and nicotinamide adenine dinucleotide (NAD

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L-(−)-Glucose, ≥99%
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5-Amino-1-methylquinolinium iodide, ≥98% (HPLC)
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6-Chloronicotinamide, 98%
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