5-amino-1MQ 50 mg

5-Amino-1MQ 50 mg research-grade lyophilized powder in a glass vial. This small-molecule compound, 5-amino-1-methylquinolinium, is investigated in experimental models as a selective inhibitor of the enzyme nicotinamide N-methyltransferase (NNMT) and a modulator of NAD+ salvage and SAM-cycle metabolism.

Research Overview

5-Amino-1MQ is a selective inhibitor of nicotinamide N-methyltransferase (NNMT), used in laboratory studies to probe mechanisms of cellular energy metabolism, NAD+ salvage and S-adenosylmethionine (SAM) cycle flux.

Primary Research Areas

• NNMT inhibition & NAD+ metabolism: Experimental models exploring NNMT blockade and downstream NAD+ and SAM-cycle modulation [8].
• Adipocyte energy metabolism & lipogenesis suppression: In vivo models of diet-induced obesity where 5-Amino-1MQ reduces lipogenesis and methylation marker levels [4,8].
• Methylation burden & metabolic dysfunction research: Laboratory applications in cellular methylation stress, SAM-cycle imbalance and NAD+ salvage engineering [8].
• Muscle strength in old mice: in 24-month-old mice, the inhibitor raised grip strength about 40 per cent above sedentary controls and lifted peak torque in an injured leg muscle by roughly 70 per cent, with more stem-cell activity and larger fibres. Nothing similar has been tried in people [1,2].
• Fatty liver: obese mice on 28 days of 5A1MQ had less fat in the liver, fewer inflammatory macrophages there, smaller and lighter livers and lower liver triglycerides, and their ALT and AST readings returned to normal. Adding the drug to a lean diet cleared liver fat further than the diet alone [3,4].
• Blood sugar and insulin: the same 28-day course in diet-induced obese mice improved oral glucose tolerance and insulin sensitivity and brought down the high insulin levels those mice carry. This is mouse work; no one has measured glucose control in people on this compound [3].
• Gut bacteria shift: obese mice given 5-amino-1-methylquinolinium alongside a switch to low-fat food developed a distinct gut flora, with less Erysipelatoclostridium and more Lactobacillus than mice switched to the same food without the drug. Both genera are linked to body weight, though what this means for a person is unknown [5].
• Tumour growth in mice: 5-amino-1-methylquinolinium iodide slowed bladder-tumour growth in mice and made an anti-PD-L1 antibody kill more cancer cells, and in the dish it stopped HeLa cervical cancer cells dividing while apparently leaving normal HEK-293 cells alone. None of this is human treatment data [6,7].

References

1. 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. Sci Rep. 2024;14(1):15554. PMID 38969654. doi:10.1038/s41598-024-66034-9
2. 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. Biochem Pharmacol. 2019;163:481-492. PMID 30753815. doi:10.1016/j.bcp.2019.02.008
3. Babula JJ, Bui D, Stevenson HL, et al. Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. Diabetes Obes Metab. 2024;26(11):5272-5282. PMID 39161060. doi:10.1111/dom.15879
4. Sampson CM, Dimet AL, Neelakantan H, et al. Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice. Sci Rep. 2021;11(1):5637. PMID 33707534. doi:10.1038/s41598-021-85051-6
5. Dimet-Wiley A, Wu Q, Wiley JT, et al. Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice. Sci Rep. 2022;12(1):484. PMID 35013352. doi:10.1038/s41598-021-03670-5
6. Yang M, Wang B, Hou W, et al. NADmetabolism enzyme NNMT in cancer-associated fibroblasts drives tumor progression and resistance to immunotherapy by modulating macrophages in urothelial bladder cancer. J Immunother Cancer. 2024;12(7). PMID 39067875. doi:10.1136/jitc-2024-009281
7. Akar S, Duran T, Azzawri AA, et al. Small molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells. J Obstet Gynaecol. 2021;41(8):1240-1245. PMID 33645410. doi:10.1080/01443615.2020.1854696
8. Neelakantan H, Vance V, Wetzel MD, 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. PMID 29155147. doi:10.1016/j.bcp.2017.11.007