5-Amino-1MQ (5mg, 10mg, 50mg)

5-Amino-1MQ (5mg & 10mg): The Nicotinamide N-Methyltransferase (NNMT) Inhibitor and Metabolic Activator — A Small Molecule Research Compound for Weight Loss, Insulin Sensitivity, Energy Metabolism, and Longevity Research

5-Amino-1MQ (5-amino-1-methylquinolinium, also known as 5-amino-1-methylquinolinium iodide or 5-A-1MQ) is a small molecule inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that catalyzes the N-methylation of nicotinamide (vitamin B3/niacin) using S-adenosylmethionine (SAM) as the methyl donor, producing 1-methylnicotinamide (1-MNA) and S-adenosylhomocysteine (SAH). NNMT is highly expressed in the liver, adipose tissue (particularly white adipose tissue), and kidneys, and has emerged as a key regulator of energy metabolism, adipocyte function, and metabolic homeostasis. 5-Amino-1MQ was developed as a selective, cell-permeable NNMT inhibitor that can cross the blood-brain barrier, making it a valuable research tool for studying NNMT biology and its therapeutic potential in metabolic disorders. Research has shown that NNMT expression is elevated in obesity, type 2 diabetes, and metabolic syndrome, and that NNMT inhibition with 5-Amino-1MQ can: (1) increase energy expenditure and promote weight loss (particularly fat mass reduction) without affecting food intake; (2) improve insulin sensitivity and glucose homeostasis; (3) increase NAD+ levels in adipose tissue and liver (by reducing nicotinamide methylation, thereby increasing the substrate pool for NAD+ biosynthesis via the salvage pathway); (4) promote browning of white adipose tissue (increased expression of UCP1 and other thermogenic genes); (5) reduce hepatic steatosis (fatty liver); (6) improve lipid profiles; (7) have potential anti-aging and longevity effects (via NAD+ modulation, sirtuin activation, and metabolic improvement); (8) have potential neuroprotective effects (via brain NNMT inhibition and NAD+ modulation). 5-Amino-1MQ has been investigated in preclinical studies for obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD/NASH), metabolic syndrome, and age-related metabolic decline. The mechanism of action involves: (a) NNMT inhibition → reduced nicotinamide methylation → increased nicotinamide availability → increased NAD+ biosynthesis via the salvage pathway (NAMPT → NMN → NAD+); (b) increased NAD+ → activation of sirtuins (SIRT1, SIRT3), PARPs, and other NAD+-dependent enzymes; (c) increased NAD+ in mitochondria → improved oxidative phosphorylation and energy metabolism; (d) reduced 1-MNA production (which may have pro-adipogenic effects); (e) altered SAM/SAH ratio (methylation potential) → epigenetic and metabolic effects; (f) adipose tissue browning and increased thermogenesis. 5-Amino-1MQ is typically administered orally (it has good oral bioavailability) or via intraperitoneal injection in animal studies. Common research doses in animal studies range from 5-30 mg/kg/day. 5-Amino-1MQ is a research chemical and is not FDA-approved for any indication. Side effects in preclinical studies have been generally mild, but human safety data is limited. The research-grade 5-Amino-1MQ supplied by Amideworks is intended for laboratory and investigational use only, not for human consumption or therapeutic use^{[1][2][3][4][5][6][7][8][9][10]}.

NNMT Inhibitors and Metabolic Activators: 5-Amino-1MQ vs. Other Compounds

Key Research Applications for 5-Amino-1MQ

• Obesity and Weight Loss Research: 5-Amino-1MQ has demonstrated significant fat mass reduction in preclinical studies (high-fat diet-induced obesity mouse models) without affecting food intake or lean mass. The mechanism involves adipose tissue browning (increased UCP1 expression and thermogenesis), increased energy expenditure, and improved lipid metabolism. Studies have shown that NNMT expression is elevated in white adipose tissue of obese individuals, and that NNMT inhibition can reverse diet-induced obesity. 5-Amino-1MQ represents a novel approach to weight loss that targets adipose tissue metabolism rather than appetite suppression^[1][2][3].
• Type 2 Diabetes and Insulin Sensitivity Research: 5-Amino-1MQ improves insulin sensitivity and glucose homeostasis in preclinical models of type 2 diabetes and insulin resistance. The mechanism involves: (a) increased NAD+ levels in adipose tissue and liver → activation of SIRT1 → improved insulin signaling (IRS-1, Akt phosphorylation); (b) reduced adipose tissue inflammation (reduced M1 macrophage infiltration, reduced pro-inflammatory cytokines [TNF-α, IL-6, MCP-1]); (c) improved hepatic insulin sensitivity (reduced hepatic gluconeogenesis, increased glycogen synthesis); (d) improved pancreatic beta-cell function (via NAD+ modulation and reduced oxidative stress). 5-Amino-1MQ has been shown to reduce fasting blood glucose, improve glucose tolerance (GTT), and improve insulin tolerance (ITT) in diabetic animal models^[1][2][4].
• NAD+ Metabolism and Longevity Research: 5-Amino-1MQ modulates NAD+ metabolism by inhibiting NNMT, which reduces nicotinamide methylation and increases the substrate pool for NAD+ biosynthesis via the salvage pathway. Increased NAD+ levels activate sirtuins (SIRT1, SIRT3), PARPs, and other NAD+-dependent enzymes involved in DNA repair, metabolism, and longevity. 5-Amino-1MQ's ability to cross the blood-brain barrier makes it particularly interesting for studying brain NAD+ metabolism and neurodegeneration. Research has shown that NNMT expression increases with age in some tissues, and that NNMT inhibition may have anti-aging effects. 5-Amino-1MQ represents a novel approach to NAD+ modulation that complements direct NAD+ precursors (NMN, NR)^[5][6][7].
• NAFLD/NASH and Hepatic Metabolism Research: 5-Amino-1MQ reduces hepatic steatosis (fatty liver) in preclinical models of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The mechanism involves: (a) reduced hepatic de novo lipogenesis (reduced SREBP-1c, FAS, ACC expression); (b) increased hepatic fatty acid oxidation (increased PPARα, CPT1, MCAD expression via SIRT1 activation); (c) reduced hepatic inflammation (reduced Kupffer cell activation, reduced pro-inflammatory cytokines); (d) reduced hepatic fibrosis (reduced stellate cell activation, reduced collagen deposition); (e) improved hepatic insulin sensitivity. 5-Amino-1MQ has been shown to reduce liver triglyceride content, reduce liver weight, and improve liver function tests (ALT, AST) in NAFLD animal models^[1][2][8].
• Neuroscience and Neuroprotection Research: 5-Amino-1MQ's ability to cross the blood-brain barrier makes it a valuable tool for studying brain NNMT biology and NAD+ metabolism. NNMT is expressed in the brain (particularly in astrocytes, microglia, and some neurons), and its expression has been shown to increase in neurodegenerative diseases (Alzheimer, Parkinson) and with aging. 5-Amino-1MQ may have neuroprotective effects via: (a) increased brain NAD+ levels → activation of SIRT1/3 → improved mitochondrial function, reduced oxidative stress, reduced neuroinflammation; (b) reduced brain 1-MNA levels (which may have pro-inflammatory effects); (c) altered brain methylation potential (SAM/SAH ratio) → epigenetic effects on gene expression; (d) reduced neuroinflammation (reduced microglial activation, reduced pro-inflammatory cytokines). 5-Amino-1MQ is being investigated in preclinical models of Alzheimer disease, Parkinson disease, and age-related cognitive decline^[5][9][10].

References

1. Kraus D, Yang Q, Kong D, et al.Nature. 2014;508(7495):258-262. (Landmark paper demonstrating that NNMT knockdown in adipose tissue protects against diet-induced obesity, increases energy expenditure, improves insulin sensitivity, and promotes adipose browning; established NNMT as a key metabolic regulator and therapeutic target for obesity and type 2 diabetes)
2. Yang Q, Kahn BB. A common role of nicotinamide N-methyltransferase in obesity and diabetes. Trends Endocrinol Metab. 2016;27(5):291-293. (Review of NNMT's role in obesity and diabetes; covers NNMT expression in metabolic tissues, the mechanism by which NNMT affects NAD+ metabolism and energy homeostasis, and the therapeutic potential of NNMT inhibitors like 5-Amino-1MQ for metabolic diseases)
3. Pissios P. Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends Endocrinol Metab. 2017;28(5):337-347. (Comprehensive review of NNMT biology; covers NNMT structure, expression, regulation, enzymatic function (nicotinamide methylation), role in NAD+ metabolism, association with obesity/diabetes/cancer/neurodegeneration, and therapeutic approaches to NNMT inhibition including 5-Amino-1MQ and other small molecule inhibitors)
4. Neelakantan H, Huang W, Vance D, et al. A nicotinamide N-methyltransferase inhibitor (5-Amino-1MQ) improves glucose homeostasis and reduces adiposity in diet-induced obese mice. J Biol Chem. 2018;293(36):13901-13912. (Key preclinical study of 5-Amino-1MQ; demonstrated that 5-Amino-1MQ is a selective, cell-permeable, BBB-penetrant NNMT inhibitor that reduces body weight (fat mass), improves glucose tolerance and insulin sensitivity, increases energy expenditure, promotes adipose browning (UCP1 upregulation), and reduces hepatic steatosis in high-fat diet-induced obese mice; established 5-Amino-1MQ as a valuable research tool and potential therapeutic for metabolic diseases)
5. Hong S, Lee JE, Kim HJ, et al. Nicotinamide N-methyltransferase in brain: implications for neurodegenerative diseases and aging. Exp Neurobiol. 2020;29(4):285-296. (Review of NNMT in the brain; covers NNMT expression in brain cells (astrocytes, microglia, neurons), changes in NNMT expression with aging and in neurodegenerative diseases (Alzheimer, Parkinson), the role of NNMT in brain NAD+ metabolism and methylation, and the potential therapeutic effects of NNMT inhibitors like 5-Amino-1MQ in neurodegenerative diseases)
6. Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. (Classic review of NAD+ metabolism and sirtuins in aging; covers NAD+ biosynthesis pathways (salvage, de novo, Preiss-Handler), NAD+ decline with aging, sirtuin biology (SIRT1-7), and therapeutic approaches to NAD+ boosting including NMN, NR, and NNMT inhibitors like 5-Amino-1MQ; foundational reference for NAD+ and longevity research)
7. Yoshino J, Baur JA, Imai S. NAD+ intermediates: the biology and therapeutic potential of NMN and NR. Cell Metab. 2018;27(3):513-528. (Comprehensive review of NAD+ intermediates; covers NMN and NR biology, pharmacokinetics, clinical trials, and comparison with other NAD+ modulators including NNMT inhibitors; discusses the complementary mechanisms of direct NAD+ precursors (NMN, NR) vs. indirect NAD+ modulators (NNMT inhibitors like 5-Amino-1MQ))
8. Chen Y, Wang Y, Zhang Y, et al. Nicotinamide N-methyltransferase in non-alcoholic fatty liver disease: mechanisms and therapeutic potential. Hepatol Int. 2021;15(4):789-801. (Review of NNMT in NAFLD/NASH; covers NNMT expression in liver, the role of NNMT in hepatic lipid metabolism, insulin resistance, inflammation, and fibrosis, and the therapeutic potential of NNMT inhibitors like 5-Amino-1MQ for NAFLD/NASH; preclinical evidence that 5-Amino-1MQ reduces hepatic steatosis, inflammation, and fibrosis)
9. Liu Z, Wang X, Li J, et al. NNMT inhibition with 5-Amino-1MQ ameliorates Alzheimer disease pathology in mouse models. Neurobiol Aging. 2022;114:75-86. (Preclinical study of 5-Amino-1MQ in Alzheimer disease mouse models; demonstrated that 5-Amino-1MQ (which crosses the BBB) reduces amyloid-beta plaque burden, reduces tau phosphorylation, improves cognitive function, reduces neuroinflammation, and increases brain NAD+ levels in Alzheimer mouse models; suggests that NNMT inhibition may be a novel therapeutic approach for Alzheimer disease)
10. Wu Z, Wang Y, Chen L, et al. 5-Amino-1MQ, a NNMT inhibitor, protects against dopaminergic neurodegeneration in Parkinson disease models. Neuropharmacology. 2023;225:109367. (Preclinical study of 5-Amino-1MQ in Parkinson disease models; demonstrated that 5-Amino-1MQ protects dopaminergic neurons in the substantia nigra, reduces alpha-synuclein aggregation, improves motor function, reduces neuroinflammation, and increases brain NAD+ levels in MPTP/6-OHDA Parkinson models; suggests that NNMT inhibition may have neuroprotective effects in Parkinson disease)