5-Amino-1-methylquinolinium (5-Amino-1MQ) is a cell-permeable small molecule inhibitor of nicotinamide N-methyltransferase (NNMT), a cytosolic enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to nicotinamide, producing 1-methylnicotinamide (1-MNA) and S-adenosylhomocysteine (SAH). NNMT has emerged as a major metabolic regulator because it sits at the intersection of two critical cellular metabolic pathways: the NAD+ salvage pathway and the methyl donor cycle.
By inhibiting NNMT, 5-Amino-1MQ produces two simultaneous metabolic effects. First, it preserves nicotinamide for recycling through the NAD+ salvage pathway (nicotinamide → NAMPT → NMN → NAD+), increasing intracellular NAD+ levels and thereby enhancing sirtuin (SIRT1-7) and PARP enzyme activity. Second, it preserves the cellular SAM/SAH ratio (methylation potential), maintaining SAM-dependent histone and DNA methyltransferase activity. Published gene expression studies demonstrate that NNMT inhibition reprograms adipocyte gene expression from a lipogenic phenotype to an oxidative phenotype through altered histone methylation marks — this is an epigenetic mechanism of metabolic regulation.
NNMT is overexpressed in white adipose tissue of obese individuals, where it acts as a metabolic brake — diverting nicotinamide away from NAD+ synthesis and depleting SAM-dependent methylation capacity. Published research in diet-induced obesity models has shown that NNMT inhibition reduces adipocyte size, increases whole-body energy expenditure, and improves metabolic parameters. The compound is cell-permeable and does not require specialized delivery in cell culture experiments.
Supplied as a lyophilized powder with ≥99% purity. Store at -20°C desiccated. For metabolic and epigenetic research only.
