5-Amino-1MQ 5mg vial

5-Amino-1MQ is a synthetic small molecule designed to inhibit the enzyme nicotinamide N-methyltransferase (NNMT). NNMT is primarily active in adipose tissue and plays a significant role in fat storage and energy metabolism. By blocking NNMT, 5-Amino-1MQ aims to enhance metabolic processes and promote fat loss.

Mechanism of Action

The primary action of 5-Amino-1MQ is the inhibition of NNMT, leading to increased levels of nicotinamide adenine dinucleotide (NAD+). Elevated NAD+ levels can activate sirtuin-1 (SIRT1), a gene associated with longevity and metabolic regulation. This activation may improve fat metabolism, increase energy expenditure, and support overall metabolic health.

5-Amino-1MQ Research

Obesity and 5-Amino-1MQ

Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme prevalent in many tissues, especially the liver and fat cells. Research in mice reveals that elevated NNMT correlates with reduced levels of the glucose transporter GLUT4, which is critical in skeletal muscle, cardiac muscle, and fat cells. GLUT4 is closely linked to blood sugar regulation and diabetes development. Mice with higher GLUT4 levels exhibit insulin sensitivity and resistance to type 2 diabetes, while low GLUT4 correlates with insulin resistance.

GLUT4 levels also influence basal metabolic rate; individuals with higher GLUT4 have faster metabolism and burn more calories. Exercise stimulates GLUT4 production, helping combat weight gain, elevated blood sugar, and insulin resistance. Importantly, NNMT and GLUT4 are closely interconnected, and targeting NNMT has emerged as a promising approach to treat obesity and diabetes. High NNMT levels are often found in fat cells of insulin-resistant animals, and manipulating NNMT can counter insulin resistance and obesity.

Human metabolism is efficient in calorie utilization, which paradoxically contributes to obesity under excess calorie intake. Reducing metabolic efficiency to increase calorie “waste” has long been a goal in obesity treatment, and NNMT’s role in this process could be key.

Mechanism of NNMT and 5-Amino-1MQ

NNMT slows calorie utilization, favoring storage in fat and glycogen. Lowering NNMT reduces the conversion of nicotinic acid into 1-methylnicotinamide (1-MNA), which affects metabolism by increasing energy expenditure and decreasing storage.

Administering 5-amino-1MQ, an NNMT inhibitor, boosts energy burning and GLUT4 expression, improving glucose clearance, reducing insulin need and resistance, lowering fat production, and enhancing metabolism. In mice, 10 days of 5-amino-1MQ resulted in a 7% body weight loss, 30% fat mass reduction, and normalized cholesterol without altering food intake.

Beyond metabolism, 5-amino-1MQ may modify fat cell function, promoting production of PAHSAs (palmitic acid esters of hydroxy-stearic acids)—lipids with anti-diabetic and anti-inflammatory properties that reduce insulin resistance and inflammation, improving cardiovascular risk.

5-Amino-1MQ and Muscle Health

In muscle, 5-amino-1MQ similarly increases GLUT4 and metabolic inefficiency, enhancing energy burn. It also stimulates muscle stem cell activation, promoting repair and growth. Studies in aged mice show treated muscles had twice the fiber size and 70% more contractile strength post-injury compared to controls. This stem cell activation could improve mobility and independence in older adults by enhancing muscle repair and function.

Elevated NNMT is linked to muscle wasting disorders such as Duchenne Muscular Dystrophy (DMD). Reducing NNMT may alleviate symptoms by promoting stem cell growth. Additionally, NNMT inhibition raises NAD+ levels, improving mitochondrial function, reducing inflammation and fibrosis, and supporting muscle and heart health in models of DMD.

Potential Cognitive Benefits

NAD+ is critical for brain energy and synaptic function. NAD+ depletion impairs neural and neuromuscular communication, impacting cognition and muscle function. Though not yet tested directly, 5-amino-1MQ’s ability to boost NAD+ suggests potential cognitive enhancement and nootropic use.

NNMT and Cancer

NNMT overexpression occurs in several cancers, including gastric, pancreatic, renal, and bladder cancers. NNMT knockout mice show resistance to these cancers, suggesting NNMT promotes tumor development. Inhibiting NNMT with compounds like 5-amino-1MQ may have therapeutic potential in cancer treatment or prevention.

Summary

5-Amino-1MQ is a membrane-permeable analogue that inhibits NNMT, a key regulator of energy metabolism linked to obesity and insulin resistance. Its inhibition leads to weight loss, improved glucose metabolism, and better cholesterol profiles in animal models. It also promotes muscle repair and may benefit neurodegenerative and muscle wasting conditions. Ongoing research explores its wider therapeutic potential, including anti-cancer effects.

Research Applications

Studies have investigated the potential therapeutic effects of 5-Amino-1MQ in various conditions associated with metabolic dysfunction, including:

• Obesity: Research suggests that 5-Amino-1MQ may reduce fat accumulation and promote fat loss.
• Type 2 Diabetes: By improving insulin sensitivity, 5-Amino-1MQ may aid in better blood sugar regulation.
• Aging: The activation of SIRT1 by increased NAD+ levels may contribute to anti-aging effects.

While these findings are promising, further research is needed to fully understand the therapeutic potential and safety profile of 5-Amino-1MQ in humans.

Safety and Usage

5-Amino-1MQ is currently available for research purposes only and is not approved for human consumption. It is typically provided in a lyophilized (powder) form to ensure maximum stability. Researchers interested in studying 5-Amino-1MQ should adhere to appropriate safety protocols and ethical guidelines.

Referenced Citations

• Kim Y-B, et al. Muscle-Specific Deletion of the Glut4 Glucose Transporter Alters Multiple Regulatory Steps in Glycogen Metabolism. Mol Cell Biol. 2005;25(21):9713-9723. doi:10.1128/MCB.25.21.9713-9723.2005 
• Carvalho E, Kotani K, Peroni OD, Kahn BB. Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle. Am J Physiol Endocrinol Metab. 2005;289(4):E551-561. doi:10.1152/ajpendo.00116.2005 
• Weight loss without effort: NNMT inhibitors. Recherche animale. Available: https://www.recherche-animale.org/en/weight-loss-without-effort-nnm-inhibitors [Accessed Mar 30, 2020] 
• Minois N, Carmona-Gutierrez D, Madeo F. Polyamines in aging and disease. Aging. 2011;3(8):716-732. 
• Neelakantan H, et al. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochem Pharmacol. 2018;147:141-152. doi:10.1016/j.bcp.2017.11.07 
• Moraes-Vieira PM, Saghatelian A, Kahn BB. GLUT4 Expression in Adipocytes Regulates De Novo Lipogenesis and Levels of a Novel Class of Lipids With Antidiabetic and Anti-inflammatory Effects. Diabetes. 2016;65(7):1808-1815. doi:10.2337/db16-0221 
• Neelakantan H, et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochem Pharmacol. 2019;163:64-71. doi:10.1016/j.bcp.2019.02.008 
• Pissios P. Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends Endocrinol Metab. 2017;28(5):340-353. doi:10.1016/j.tem.2017.02.004 
• Ryu D, et al. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Sci Transl Med. 2016;8(361):361ra139. doi:10.1126/scitranslmed.aaf5504 
• Lund S, Zhang N, Wang X, Polo-Parada L, Ding S. The effect of NAMPT deletion in projection neurons on the function and structure of neuromuscular junction (NMJ) in mice. Sci Rep. 2020;10(1):1-15. doi:10.1038/s41598-019-57085-4