5-Amino-1MQ 50mg Capsules

5-Amino-1MQ (5-amino-1-methylquinolin-2(1H)-one) is a synthetic small molecule that functions as a selective inhibitor of the enzyme nicotinamide N-methyltransferase (NNMT). By inhibiting NNMT, 5-Amino-1MQ increases the levels of nicotinamide adenine dinucleotide (NAD+), a cofactor central to cellular metabolism. This elevation in NAD+ activates sirtuin-1 (SIRT1), a protein associated with various metabolic processes, including fat metabolism and energy production.

5-Amino-1MQ Research

Obesity and Nicotinamide N-Methyltransferase (NNMT)

Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme found throughout the body, with the highest levels in the liver and fat cells. Research in mice shows that elevated NNMT levels are associated with decreased expression of the glucose transporter GLUT4. GLUT4, primarily found in skeletal and cardiac muscle as well as fat cells, plays a crucial role in regulating blood sugar levels and the development of diabetes. Rodent studies indicate that mice with high GLUT4 expression are insulin sensitive and relatively resistant to type 2 diabetes, whereas mice with low GLUT4 levels display severe insulin resistance.

GLUT4 is also linked to basal metabolic rate and the concept of "fast" versus "slow" metabolism. Individuals with naturally higher GLUT4 levels tend to have a faster metabolism, burning more calories. Exercise stimulates GLUT4 production, helping to combat weight gain, high blood sugar, and insulin resistance. Importantly, NNMT and GLUT4 are closely connected and jointly influence basal metabolism in mammals. 

According to Dr. Barbara Kan of Harvard Medical School, the link between GLUT4 and NNMT spurred investigation of NNMT as a potential target for treating diabetes and obesity. High NNMT levels are commonly found in the fat cells of insulin-resistant animals, and manipulating this gene can counteract insulin resistance and profoundly affect weight and obesity.

Human and animal metabolism are highly efficient, maximizing calorie utilization. Unfortunately, this efficiency may contribute to obesity when calorie intake is excessive. Reducing metabolic efficiency, effectively causing the body to "waste" calories, has long been a therapeutic goal in addressing obesity. NNMT’s interaction with GLUT4 may be the key to unlocking this strategy.

At a basic level, NNMT slows the rate at which the body burns calories, leaving more available for storage as fat or glycogen. Reducing NNMT levels decreases the conversion of nicotinic acid (NA) into 1-methylnicotinamide (1-MNA), which influences metabolism in two key ways.

Administering an NNMT inhibitor such as 5-amino-1-methylquinolinium (5-amino-1MQ) results in increased energy expenditure and reduced energy storage. Additionally, decreased NNMT boosts GLUT4 expression, improving glucose clearance from the blood and its subsequent utilization. This leads to reduced insulin demand, decreased insulin resistance, less fat production, and enhanced energy metabolism. In mouse studies, just 10 days of 5-amino-1MQ treatment produced a 7% reduction in body weight and a 30% reduction in fat mass without altering food intake. Treated mice also displayed cholesterol levels comparable to non-obese controls.

Emerging evidence suggests that 5-amino-1MQ’s benefits extend beyond NNMT inhibition and GLUT4 upregulation. Research in mice shows that increasing GLUT4 expression alters fat cell function, promoting the production of palmitic acid esters of hydroxy-stearic acids (PAHSAs). PAHSAs are lipids with anti-diabetic and anti-inflammatory properties that reduce insulin resistance and inflammation, improving cardiovascular risk profiles. Though this is a newer area of research, it hints at expanded therapeutic potential for 5-amino-1MQ.

5-Amino-1MQ and Muscle Function

5-amino-1MQ also impacts skeletal muscle by increasing GLUT4 receptor production and metabolic inefficiency, boosting energy expenditure. Recent mouse studies reveal that NNMT inhibition—including via 5-amino-1MQ—enhances muscle repair by stimulating stem cell activation. In aged (24-month-old) mice, NNMT inhibitors increased muscle stem cell activity after injury, leading to myofibers twice as large in cross section and improved contractile strength. Treated mice showed 70% greater muscle force post-healing compared to controls.

Stimulating muscle stem cells may improve mobility and independence in older adults by accelerating repair and reducing risks like falls, significantly enhancing quality of life.

Increased NNMT expression is also linked to muscle wasting disorders such as Duchenne Muscular Dystrophy (DMD). Reducing NNMT may alleviate symptoms by promoting stem cell growth and division. The exact mechanisms are not fully understood but likely involve elevated NAD+ levels due to NNMT inhibition. Boosting NAD+ through compounds like 5-amino-1MQ improves muscle function, heart pathology, and DMD symptoms in animal models, primarily via enhanced mitochondrial function and reduced inflammation and fibrosis.

Potential Cognitive Effects of 5-Amino-1MQ

NAD+ is critical for brain energy metabolism. NAD+ depletion is associated with cognitive impairments and impacts synaptic transmission and neuromuscular junction function. Mouse studies link NAD+ deficits to reduced cognitive and muscle function. While 5-amino-1MQ has not been specifically tested for cognitive effects, it is likely to increase brain NAD+ levels as it does in other tissues, suggesting potential as a treatment for cognitive dysfunction or as a nootropic to enhance cognition in healthy individuals. Research into these possibilities is ongoing.

NNMT and Cancer

NNMT expression is elevated in various cancers, including gastric, pancreatic, renal, and bladder cancers. Mice lacking the NNMT gene show resistance to developing these cancers, implicating NNMT as a possible causal factor. While research is ongoing, NNMT inhibition may emerge as a strategy to treat or prevent certain cancers or reduce their aggressiveness. Whether 5-amino-1MQ’s NNMT inhibition translates into anticancer effects remains to be determined.

5-Amino-1MQ Summary

5-amino-1MQ is a small, membrane-permeable analogue of naturally occurring methylquinolinium that inhibits nicotinamide N-methyltransferase (NNMT). NNMT is a key enzyme in cellular energy metabolism, closely tied to weight control and insulin resistance. In animal studies, 5-amino-1MQ reduces weight, improves insulin sensitivity, and lowers plasma cholesterol. It also regulates muscle and nerve function, with promising implications for muscular dystrophy and age-related muscle wasting. Additionally, NNMT inhibition correlates with reduced cancer aggressiveness in various types. Overall, 5-amino-1MQ is a promising molecule targeting metabolic disease, muscle health, and possibly cancer.

Research Applications

5-Amino-1MQ is primarily utilized in scientific studies focusing on:

• Fat Metabolism: Investigating its role in enhancing fat breakdown and promoting fat loss.
• Energy Metabolism: Exploring its effects on increasing energy expenditure and improving mitochondrial function.
• Muscle Preservation: Assessing its potential to preserve muscle mass during weight loss.
• Metabolic Disorders: Studying its impact on conditions such as obesity and type 2 diabetes.

Product Specifications

• Form: Lyophilized (freeze-dried) powder encapsulated in capsules.
• Dosage: Each capsule contains 50mg of 5-Amino-1MQ.
• Quantity: Typically available in bottles containing 30 or 60 capsules.
• Purity: ≥99%, ensuring high-quality material for research purposes.
• Packaging: Sealed bottles to maintain product integrity.
• Storage: Store in a cool, dry place away from direct sunlight.

Safety and Handling

5-Amino-1MQ is intended strictly for laboratory research and is not approved for human consumption. Handle with care, following appropriate safety protocols. Ensure proper storage conditions to maintain the integrity and efficacy of the compound.

Referenced Citations

• Y.-B. Kim et al., “Muscle-Specific Deletion of the GLUT4 Glucose Transporter Alters Multiple Regulatory Steps in Glycogen Metabolism,” Mol. Cell. Biol., vol. 25, no. 21, pp. 9713–9723, Nov. 2005, doi:10.1128/MCB.25.21.9713-9723.2005. 
• E. Carvalho, K. Kotani, O. D. Peroni, and B. B. Kahn, “Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle,” Am. J. Physiol. Endocrinol. Metab., vol. 289, no. 4, pp. E551–561, Oct. 2005, doi:10.1152/ajpendo.00116.2005. 
• “Weight loss without effort: NNMT inhibitors,” Recherche Animale. https://www.recherche-animale.org/en/weight-loss-without-effort-nnmt-inhibitors (accessed Mar. 30, 2020).
• N. Minois, D. Carmona-Gutierrez, and F. Madeo, “Polyamines in aging and disease,” Aging, vol. 3, no. 8, pp. 716–732, Aug. 2011. 
• H. Neelakantan et al., “Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice,” Biochem. Pharmacol., vol. 147, pp. 141–152, Jan. 2018, doi:10.1016/j.bcp.2017.11.007. 
• P.M. Moraes-Vieira, A. Saghatelian, and B. B. Kahn, “GLUT4 Expression in Adipocytes Regulates De Novo Lipogenesis and Levels of a Novel Class of Lipids With Antidiabetic and Anti-inflammatory Effects,” Diabetes, vol. 65, no. 7, pp. 1808–1815, Jul. 2016, doi:10.2337/db16-0221. 
• H. Neelakantan et al., “Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle,” Biochem. Pharmacol., vol. 163, Feb. 2019, doi:10.1016/j.bcp.2019.02.008. 
• P. Pissios, “Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme,” Trends Endocrinol. Metab., vol. 28, no. 5, pp. 340–353, May 2017, doi:10.1016/j.tem.2017.02.004. 
• D. Ryu et al., “NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation,” Sci. Transl. Med., vol. 8, no. 361, p. 361ra139, Oct. 2016, doi:10.1126/scitranslmed.aaf5504. 
• S. Lundt, N. Zhang, X. Wang, L. Polo-Parada, and S. Ding, “The effect of NAMPT deletion in projection neurons on the function and structure of neuromuscular junction (NMJ) in mice,” Sci. Rep., vol. 10, Jan. 2020, doi:10.1038/s41598-019-57085-4.