5-Amino-1MQ

5-Amino-1MQ research compound (5-amino-1-methylquinolinium) is a selective, membrane-permeable small molecule inhibitor of nicotinamide N-methyltransferase (NNMT) — an enzyme highly expressed in liver, white adipose tissue, skeletal muscle, kidney, and brain that catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to nicotinamide, generating 1-methylnicotinamide (1-MNA) as its primary reaction product. In vitro, 5-amino-1MQ significantly reduced intracellular 1-MNA, increased intracellular NAD+, and suppressed lipogenesis in adipocytes; in vivo, treated mice showed significantly reduced body weights, white adipose masses, and adipocyte sizes without significant impact on food intake or observable adverse effects. PubMed Central By intercepting this methylation step, 5-amino-1MQ preserves nicotinamide for rerouting into the NAD+ salvage pathway — a mechanism entirely distinct from NAD+ precursor supplementation approaches such as NMN or NR — thereby elevating intracellular NAD+ levels and supporting mitochondrial oxidative phosphorylation efficiency. In diet-induced obese mouse models treated once daily for 28 days, 5A1MQ dose-dependently limited body weight and fat mass gain without altering food intake or lean mass, while also improving liver histopathology and circulating metabolic biomarkers, validating NNMT inhibition as a pharmacological approach to ameliorate obesity-linked metabolic imbalances. PubMed Central Furthermore, in aged skeletal muscle models, NNMT inhibitor-treated aged sedentary mice showed approximately 40% greater grip strength than sedentary controls, while the combination of NNMT inhibition with intensive exercise produced additive improvements in grip strength, running capacity, and muscle physiology through molecular mechanisms distinct from exercise training alone. Nature Additionally, NNMT inhibition has been shown to preserve SAM methyl-donor pools, supporting histone methylation capacity and epigenetic maintenance, positioning 5-amino-1MQ as a multi-pathway metabolic and cellular aging research tool.

• NNMT enzyme inhibition and nicotinamide methylation pathway studies
• NAD+ salvage pathway preservation and intracellular NAD+ elevation research
• Adipose tissue metabolism, lipogenesis suppression, and adipocyte size investigations
• Diet-induced obesity and metabolic dysfunction preclinical model evaluations
• Insulin sensitivity, glucose homeostasis, and Type 2 diabetes mechanism research
• SAM methyl-donor pool conservation and epigenetic regulation studies
• Sarcopenia, skeletal muscle function, and age-related muscle deterioration models
• Mitochondrial efficiency, oxidative phosphorylation, and cellular energy metabolism research

• Neelakantan H et al. Biochem Pharmacol. 2019;158:262–271.

• Babula JJ, Bui D, Stevenson HL, Watowich SJ, Neelakantan H.

• Dimet-Wiley AL, Latham CM, Brightwell CR, et al. Sci Rep. 2024;14(1):15554.

• Dimet-Wiley A, Wu Q, Wiley JT, et al. Sci Rep. 2022;11(1):5637.
• Kannt A et al. Sci Rep. 2015;5:8168.