5-Amino-1MQ is a small molecule currently studied for its effects on cellular metabolism and energy regulation. It functions as a selective inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that influences nicotinamide adenine dinucleotide (NAD⁺) levels and plays a role in fat metabolism, insulin sensitivity, and muscle energy balance. By modulating NNMT activity, 5-Amino-1MQ has been observed in preclinical studies to enhance cellular NAD⁺ availability, promote lipid metabolism, and improve mitochondrial efficiency. Researchers are exploring its potential to support investigations into obesity, metabolic health, and age-related decline.
5-Amino-1MQ (5-Amino-1-methylquinolinium) is a methyltransferase inhibitor under active study for its metabolic and cellular regulatory properties. It is part of a growing class of compounds aimed at understanding how NNMT inhibition can influence energy expenditure and adipose tissue function. NNMT regulates the methylation of nicotinamide, a precursor to NAD⁺, which is central to cellular redox balance and mitochondrial energy production. Elevated NNMT expression has been associated with obesity, insulin resistance, and muscular degeneration, making this enzyme a target of interest for researchers studying metabolic disorders.
In preclinical research, 5-Amino-1MQ administration has been associated with increased intracellular NAD⁺ levels and improved energy metabolism. In murine models of diet-induced obesity, NNMT inhibition resulted in reduced fat mass and improved insulin sensitivity without requiring caloric restriction. Further cellular studies suggest that 5-Amino-1MQ enhances mitochondrial biogenesis, optimizes ATP production, and improves glucose uptake, indicating potential applications in exploring mechanisms of metabolic homeostasis, aging, and muscle regeneration.
Beyond its metabolic implications, NNMT inhibition is being investigated for potential effects on muscle function, neuronal repair, and vascular health. Some studies have also suggested a role in modulating inflammatory signaling and oxidative stress. The small molecular structure of 5-Amino-1MQ enables efficient cell penetration, allowing researchers to study its biochemical effects across multiple tissue types.
All findings to date are preclinical. No human studies have yet validated the compound’s safety or pharmacokinetics. Its use remains limited to controlled laboratory research designed to elucidate molecular mechanisms underlying metabolic regulation and NAD⁺ metabolism.
Research & References:
Research into 5-Amino-1MQ began after the discovery that NNMT activity contributes to energy imbalance and metabolic dysfunction. Neelakantan et al. (2018) demonstrated that inhibiting NNMT using small molecules like 5-Amino-1MQ reversed obesity and improved insulin sensitivity in mice without changes in food intake. The compound’s mechanism involves increasing levels of nicotinamide and NAD⁺, which enhances mitochondrial efficiency and cellular energy utilization.
Subsequent studies expanded the understanding of NNMT’s influence on systemic metabolism. In models of aging and muscle degeneration, NNMT inhibition activated dormant muscle stem cells, leading to improved regenerative potential and reduced muscle fatigue. Additional work by Pissios (2017) and Ryu et al. (2016) linked NNMT regulation with the NAD⁺ salvage pathway, showing that restoring NAD⁺ availability could protect against age-related metabolic decline and improve muscle and liver function.
5-Amino-1MQ’s role as an epigenetic modulator has also been proposed, given NNMT’s influence on methyl group utilization and histone methylation. This positions the molecule as a potential tool for studying the intersection of metabolism, gene expression, and aging biology.
Overall, the compound provides researchers with a promising model for exploring NAD⁺ metabolism, metabolic health, and cellular regeneration. Its preclinical profile highlights its potential as a valuable investigative molecule in metabolic and biochemical research.
- Neelakantan, H. et al. (2018). “Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high-fat diet-induced obesity in mice.” Biochemical Pharmacology, 147, 141–152. DOI:10.1016/j.bcp.2017.11.007
- Pissios, P. (2017). “Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme.” Trends in Endocrinology & Metabolism, 28(5), 340–353. DOI:10.1016/j.tem.2017.02.004
- Ryu, D. et al. (2016). “NAD⁺ repletion improves muscle function in muscular dystrophy and counters global PARylation.” Science Translational Medicine, 8(361), 361ra139. DOI:10.1126/scitranslmed.aaf5504
