5-Amino-1MQ

5-Amino-1MQ (5-amino-1-methylquinolin-2(1H)-one) is a small molecule inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that methylates nicotinamide using S-adenosyl-L-methionine (SAM) as the methyl donor. NNMT is highly expressed in white adipose tissue, and its overexpression has been associated in preclinical models with adiposity-parameter shifts and metabolic-parameter dysregulation markers. By inhibiting NNMT, 5-Amino-1MQ is proposed to increase the intracellular availability of NAD+ (nicotinamide adenine dinucleotide) and SAM, two critical cofactors involved in cellular energy metabolism and epigenetic regulation.

Preclinical research published by Neelakantan and colleagues characterized 5-Amino-1MQ in diet-induced rodent research models, reporting shifts in body-mass and white-adipose-tissue parameter readouts without effects on food-intake markers. The mechanism was attributed to increased cellular energy expenditure through enhanced NAD+ availability, which activates sirtuin-dependent metabolic pathways. Additionally, NNMT inhibition was shown to reduce lipogenesis in adipocyte cell lines and to alter the expression of genes involved in lipid metabolism and adipocyte differentiation.

The relationship between NNMT and metabolic regulation extends beyond adipose tissue. Research has identified NNMT as a regulator of the methionine cycle and one-carbon metabolism, with implications for epigenetic regulation through SAM-dependent methylation reactions. Studies have also explored NNMT's role in cancer metabolism, where the enzyme is overexpressed in several tumor types and may contribute to metabolic reprogramming.