Research Applications
Metabolic Regulation and Fat Loss
5-Amino-1MQ demonstrates remarkable efficacy in reversing diet-induced obesity and reducing body fat accumulation through metabolic modulation rather than appetite suppression. Research published in Biochemical Pharmacology demonstrates that systemic administration of 5-Amino-1MQ to diet-induced obese mice produced approximately 5.1% body weight loss and 35% reduction in white adipose tissue mass over 11 days of treatment, without affecting total food intake. This weight loss occurred exclusively through enhanced metabolic efficiency and increased energy expenditure.
Mechanistic studies reveal that 5-Amino-1MQ treatment decreases adipocyte size by over 30% and reduces adipocyte volume by more than 40% compared to untreated obese controls. The compound suppresses lipogenesis in a concentration-dependent manner, with doses of 30-60 µM reducing lipid accumulation by 50-70% in cultured adipocytes. Treatment also produces beneficial changes in plasma lipid profiles, decreasing total cholesterol levels by approximately 30%, bringing these values to levels comparable with normal-weight controls.
The metabolic benefits extend to cellular energy regulation, where NNMT inhibition increases intracellular NAD+ levels by 1.2-1.6 fold. This elevation in NAD+ activates SIRT1, a master regulator of metabolic pathways that promotes fat oxidation, enhances mitochondrial function, and improves insulin sensitivity. Studies demonstrate that 5-Amino-1MQ increases energy expenditure at the cellular level, enabling the body to burn more calories at rest without stimulant effects or cardiovascular stress.
Sources:
- Kraus D, et al. "Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice." Biochemical Pharmacology. 2018;163:481-492. https://pmc.ncbi.nlm.nih.gov/articles/PMC5826726/
- Kannt A, Pfenninger A. "Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance." Diabetologia. 2015;58(4):799-808. https://pubmed.ncbi.nlm.nih.gov/25596852/
Muscle Regeneration and Stem Cell Activation
Groundbreaking research demonstrates that 5-Amino-1MQ powerfully enhances muscle regeneration in aged skeletal muscle by reactivating senescent muscle stem cells (satellite cells). Studies published in Biochemical Pharmacology show that NNMT expression increases significantly with aging in skeletal muscle tissue and correlates with impaired muscle stem cell function and reduced regenerative capacity.
Treatment of 24-month-old mice (equivalent to elderly humans) with NNMT inhibitors rescued age-related deficits in muscle stem cell activity. Results revealed that muscle stem cell proliferation and fusion were substantially elevated in treated aged mice, supporting nearly twofold greater myofiber cross-sectional area and shifts in fiber size distribution toward larger, healthier muscle fibers. Prolonged treatment further augmented myofiber regeneration, with treated mice showing increasingly larger fiber cross-sectional areas compared to untreated aged controls.
Most remarkably, the enhanced muscle stem cell activity translated to dramatic improvements in functional muscle performance. Aged mice treated with NNMT inhibitors demonstrated approximately 70% greater peak torque (contractile force) in injured muscles compared to untreated controls. This improvement in strength was accompanied by enhanced muscle endurance and accelerated recovery from muscle injury, indicating comprehensive restoration of muscle function rather than isolated effects.
The mechanism involves restoration of NAD+ levels in aging muscle tissue, which reverses muscle stem cell senescence and dysfunction. By elevating NAD+ and activating SIRT1, 5-Amino-1MQ promotes the proliferation and differentiation of muscle stem cells into fusion-competent myoblasts, facilitating effective muscle repair and regeneration. These findings establish NNMT inhibition as a viable pharmacological approach to combat sarcopenia and age-related muscle decline.
Sources:
- Neelakantan H, Brightwell CR, Graber TG, et al. "Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle." Biochemical Pharmacology. 2019;163:481-492. https://pubmed.ncbi.nlm.nih.gov/30753815/
- Dimet-Wiley AL, Latham CM, Brightwell CR, et al. "Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice." Scientific Reports. 2024;14(1):15554. https://www.nature.com/articles/s41598-024-66034-9
Muscle Strength, Endurance and Exercise Performance
5-Amino-1MQ produces significant enhancements in muscle strength and physical performance, particularly in aged subjects where exercise capacity typically declines. Research published in Scientific Reports demonstrates that aged mice treated with NNMT inhibitors showed approximately 40% greater grip strength compared to untreated controls, remarkably surpassing even the benefits achieved through intensive exercise alone, which produced only 20% improvement.
In studies combining NNMT inhibition with progressive weighted wheel running (an intensive concurrent endurance and resistance exercise protocol), treated mice exhibited sustained enhanced muscle performance suggesting reduced need for recovery between exercise sessions. Daily running distances increased by approximately 150% in exercised mice receiving 5-Amino-1MQ treatment, compared to 75% increase in exercise-only groups, with the treatment group maintaining elevated performance more consistently over the 8-week study period.
The improvements in performance correlate with favorable changes in muscle composition and metabolic capacity. Treated mice showed increased proportions of larger, healthier muscle fibers and decreased intramyocellular lipid content, indicating enhanced fat oxidation capacity within muscle tissue. Proteomic analyses revealed that NNMT inhibition uniquely upregulated proteins involved in translation initiation, ribosomal biogenesis, and inflammatory regulation during muscle regeneration, suggesting multiple complementary mechanisms supporting muscle function.
The additive effects observed when combining NNMT inhibition with exercise indicate that the compound influences molecular pathways distinct from those activated by physical training alone. This synergistic relationship suggests 5-Amino-1MQ could enhance training adaptations and accelerate recovery, making it particularly valuable for maintaining muscle function in aging populations or during periods of reduced activity.
Sources:
- Dimet-Wiley AL, Latham CM, Brightwell CR, et al. "Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice." Scientific Reports. 2024;14(1):15554. https://www.nature.com/articles/s41598-024-66034-9
- Neelakantan H, Wang HY, Vance V, et al. "Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase." Journal of Medicinal Chemistry. 2017;60(12):5015-5028. https://pubmed.ncbi.nlm.nih.gov/28548833/
Aging, Cellular Health and Longevity
5-Amino-1MQ addresses fundamental mechanisms of cellular aging through restoration of NAD+ metabolism and mitochondrial function. Research demonstrates that NNMT expression increases significantly with advancing age, particularly in metabolic tissues, contributing to the progressive decline in NAD+ levels observed during aging. This age-related NAD+ depletion impairs mitochondrial energy production, reduces SIRT1 activity, compromises DNA repair mechanisms, and accelerates cellular senescence.
By inhibiting NNMT, 5-Amino-1MQ prevents the age-associated drain on NAD+ pools, effectively maintaining cellular NAD+ availability at more youthful levels. Elevated NAD+ activates sirtuins, particularly SIRT1, which function as master regulators of longevity pathways. SIRT1 activation promotes numerous anti-aging effects including enhanced mitochondrial biogenesis, improved stress resistance, reduced inflammation, and activation of cellular quality control mechanisms that remove damaged proteins and organelles.
Studies show that NNMT inhibition influences metabolic pathways associated with healthspan and longevity. By increasing SAM concentrations alongside NAD+, 5-Amino-1MQ supports proper methylation reactions essential for epigenetic regulation and gene expression control. This dual enhancement of NAD+ and SAM creates favorable conditions for cellular repair, metabolic flexibility, and stress resilience—key determinants of healthy aging.
The compound's effects on muscle stem cell rejuvenation particularly highlight its anti-aging potential. Aged muscle stem cells treated with NNMT inhibitors regain proliferative capacity and regenerative function, reversing cellular senescence that normally accumulates with age. This restoration of stem cell function represents a fundamental mechanism for maintaining tissue health and function throughout the aging process, potentially extending both healthspan and physical independence in older populations.
Sources:
Insulin Sensitivity and Glucose Metabolism
5-Amino-1MQ demonstrates significant beneficial effects on glucose homeostasis and insulin sensitivity through multiple complementary mechanisms. Research indicates that NNMT expression correlates positively with insulin resistance, with plasma levels of the NNMT product 1-methylnicotinamide associated with increased body mass index and metabolic dysfunction. NNMT inhibition addresses this metabolic impairment by enhancing cellular energy metabolism and improving insulin signaling pathways.
Studies demonstrate that 5-Amino-1MQ treatment improves glucose tolerance and reduces insulin resistance in diet-induced obese mice. The compound enhances insulin sensitivity in skeletal muscle by promoting GLUT4 transporter expression and increasing glucose uptake independent of insulin stimulation. This metabolic improvement occurs through AMPK pathway activation and increased NAD+-dependent SIRT1 activity, both of which enhance insulin receptor signaling and glucose metabolism.
The metabolic benefits extend to prevention of obesity-related comorbidities including type 2 diabetes. By reducing adipose tissue mass, improving lipid profiles, and enhancing mitochondrial function, NNMT inhibition addresses multiple pathways involved in metabolic syndrome development. Treatment reduces circulating markers of metabolic dysfunction and inflammation, creating a more favorable metabolic environment that supports insulin sensitivity and glucose regulation.
Sources:
- Liu M, Li L, Chu J, et al. "Serum N(1)-Methylnicotinamide Is Associated With Obesity and Diabetes in Chinese." Journal of Clinical Endocrinology & Metabolism. 2015;100(8):3112-3117. https://pubmed.ncbi.nlm.nih.gov/26066674/
- Kannt A, Pfenninger A, Teichert L, et al. "Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance." Diabetologia. 2015;58(4):799-808. https://pubmed.ncbi.nlm.nih.gov/25596852/
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