Research Brief
5-Amino-1MQ: Research Applications
🏋️ Obesity & Fat Loss
In diet-induziu obese (DIO) mice, 5-Amino 1MQ (20 mg/kg SC, 3× daily, 11 days) reduziu peso corporal by 5.1%, diminuiu epididymal white tecido adiposo (WAT) mass by ~35% (P<0.001), and reduziu adipocito size by >30%, all sem altering food intake. Plasma total cholesterol diminuiu ~30% (P<0.05). [2] In a longer study (32 mg/kg daily, 7 weeks), massa gorda diminuiu by 29.3%, normalizing composicao corporal to levels indistinguishable from age-matched lean controls. [9]
Veja tambem: AOD-9604 para pesquisas relacionadas sobre fat metabolismo research.
💊 Type 2 Diabetes & Metabolic Syndrome
5-Amino 1MQ melhorou oral glucose tolerance and suprimiu hyperinsulinemia in obese modelo de camundongos. It addresses the underlying metabolic dysfunction in white tecido adiposo que drives resistencia a insulina. [12]
Veja tambem: Tirzepatide para pesquisas relacionadas sobre metabolic research.
💪 Muscle Regeneration & Sarcopenia
In aged (22-month) mice, 5-Amino 1MQ (10 mg/kg daily, 8 weeks) mimicked exercise effects: sedentary treated mice showed ~40% greater grip strength do que untreated controls (P<0.001). Combined with exercise, grip strength aumentou by ~60%. Treated mice manteve a 1.8 km/day running increase na semana 8, enquanto untreated mice tapered off (P=0.0039). Intramyocellular lipid content diminuiu >30%. [10]
In aged (24-month) mice with agudo(a) muscle injury, treated animals showed nearly 2× greater myofiber cross-sectional area and ~70% aumentou peak torque (P<0.05), with aprimorou muscle stem cell (MuSC) proliferacao and fusion. [11]
🫁 Doenca Hepatica (NAFLD/NASH)
Combined diet switch + 5-Amino 1MQ aplicacao em pesquisa (28 days) normalized ALT and AST liver enzyme levels, reduziu liver weight/size and triglyceride content, atenuou hepatico(a) steatosis and macrofago infiltration. [12]
🧬 Duchenne Muscular Dystrophy (DMD)
Estudos pre-clinicos indicate que NNMT inibicao can improve muscle regeneration and function in DMD models by enhancing mitochondrial bioenergetics and reactivating dysfunctional muscle celulas-tronco. [11]
🪸 Chronic Kidney Disease (CKD)
Research targeting NNMT inibicao shows potential in reducing renal fibrose and tubular senescencia, with melhorou kidney function and slowed progressao da doenca in CKD models. [13]
🎯 Cancer (NNMT Overexpression)
NNMT is overexpresso(a) em aggressive cancers incluindo glioblastoma, ovarian cancer, and gastric cancer, driving metabolic and epigenetic remodeling que apoia tumor growth. 5-Amino 1MQ is being investigated for its potential para suprimir tumorigenesis, metastasis, and chemoresistance. [14]
⏳ Longevity & Anti-Aging
By elevating intracellular NAD+ levels and activating SIRT1, 5-Amino 1MQ is explored como um(a) experimental para retardar cellular aging, improve mitochondrial health, and prevent age-related physiological decline. [8]
Referencias
- Neelakantan H, Wang HY, Vance V, et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem, 60(12), 5015–5028, 2017.
- Neelakantan H, Brightwell CR, Graber TG, et al. Selective and membrane-permeable pequeno(a) molecule inhibitors of nicotinamide N-methyltransferase reverse alto(a) fat diet-induziu obesidade in mice. Biochem Pharmacol, 147, 141–152, 2018.
- Neelakantan H, Vance V, Wetzel MD, et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem, 60(12), 5015-5028, 2017.
- Sun WD, Zhu GY, Li J, et al. Nicotinamide N-methyltransferase (NNMT): um(a) novo(a) experimental target for metabolic syndrome. Front Pharmacol, 15, 1410479, 2024.
- World Anti-Doping Agency (WADA). The World Anti-Doping Code International Standard: Lista de Substancias Proibidas 2025. S0: Non-Approved Substances.
- Watowich SJ. SBIR Award: NNMT Inhibitor Development. National Institute on Aging (NIA), 2021.
- Awosemo O, Neelakantan H, Watowich SJ, et al. Development & Validation of LC–MS/MS Assay for 5-Amino-1-Methyl Quinolinium in Rat Plasma. J Pharm Biomed Anal, 204, 114255, 2021.
- Liu JR, Deng ZH, Zhu XJ, et al. Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes. BioMed Res Int, 2021, 9924314, 2021.
- Sampson CM, Dimet AL, Neelakantan H, et al. Combined nicotinamide N-methyltransferase inibicao and reduziu-calorie diet normalizes composicao corporal in camundongos obesos. Sci Rep, 11(1), 5637, 2021.
- Dimet-Wiley AL, Latham CM, Brightwell CR, et al. Nicotinamide N-methyltransferase inibicao mimics and boosts exercise-mediated improvements in muscle function in camundongos idosos. Sci Rep, 14(1), 15554, 2024.
- Neelakantan H, Vance V, Wang HYL, et al. Small molecule nicotinamide N-methyltransferase inhibitor ativa senescent muscle celulas-tronco and melhora regenerative capacity of aged musculo esqueletico. Biochem Pharmacol, 163, 481–492, 2019.
- Babula J, Dimet-Wiley AL, Seyoum B, et al. Nicotinamide N-methyltransferase inibicao mitiga obesidade-related metabolic dysfunction. Diabetes Obes Metab, 26(11), 5272–5282, 2024.
- Li XY, Pi YN, Chen Y, et al. Nicotinamide N-Methyltransferase: A Promising Biomarker and Target for Human Cancer Therapy. Front Oncol, 12, 894744, 2022.
- Moody TW, Nuche-Berenguer B, Jensen RT. Cancer and NNMT overexpression in aggressive tumors. Curr Opin Endocrinol Diabetes Obes, 2022.
- Dimet-Wiley A, Sampson CM, Neelakantan H, et al. Reduced calorie diet combined with NNMT inibicao estabelece a distinct microbiome in DIO mice. Sci Rep, 12(1), 484, 2022.
- Dong G, Latham CM, Brightwell CR, et al. Nicotinamide N-methyltransferase inibicao melhora limb function in experimental periferico(a) artery disease. Acta Physiol, 2025.
- Watowich S, Neelakantan H, McHardy SF. Quinoline derived pequeno(a) molecule inhibitors of nicotinamide N-methyltransferase (NNMT) and uses thereof. U.S. Patent No. 12,071,409, August 27, 2024.
- Watowich S, Neelakantan H, McHardy SF. Quinoline derived pequeno(a) molecule inhibitors of nicotinamide N-methyltransferase (NNMT) and uses thereof. U.S. Patent No. 11,401,243, August 2, 2022.
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