What it is
5-Amino-1MQ (5-amino-1-methylquinolinium) is a small quinolinium molecule, not a peptide, designed to block the enzyme nicotinamide N-methyltransferase (NNMT). It came out of a medicinal chemistry program at the University of Texas Medical Branch led by Stanley Watowich and Harshini Neelakantan, which screened a series of NNMT inhibitors for selectivity and cell permeability. It is often marketed alongside peptides, but chemically it is unrelated to them.
Mechanism of action
NNMT transfers a methyl group from S-adenosylmethionine (SAM) to nicotinamide, a form of vitamin B3, producing 1-methylnicotinamide. Doing so consumes SAM and removes nicotinamide that cells could otherwise recycle into NAD+, a coenzyme central to energy metabolism and to the activity of sirtuin enzymes. NNMT expression is raised in fat tissue in obesity and in aging skeletal muscle, and Neelakantan et al. (2019) linked its overexpression with age to impaired NAD+ salvage, dysregulated SIRT1 activity and senescence of muscle stem cells. 5-Amino-1MQ is described as a selective, membrane-permeable inhibitor that binds the enzyme's substrate site. Reviews attribute its effects in obese mice to shifts in the NAD+ salvage and SAM-dependent pathways, and in C2C12 muscle cells the inhibitor changed the NAD+/NADH redox state. These mechanisms come from mouse and cell work; enzyme inhibition and NAD+ changes have not been measured in people.
What it’s most studied for
Research on 5-amino-1MQ has two threads, both in mice. The larger one is obesity and metabolism: diet-induced obese mice given the inhibitor alone, or combined with a switch to a lower-fat diet, with endpoints such as body weight, white fat mass, adipocyte size, glucose tolerance, insulin sensitivity and liver fat. The second thread is aging muscle, where the question is whether blocking NNMT reactivates stem cells in injured muscle of old mice. Interest outside the laboratory comes mainly from body-composition marketing, which runs well ahead of the evidence: the published studies found for this summary are all preclinical and come from the group that developed the compound.
Notable findings
Each finding carries the species or population it was observed in and the dose that study used. Doses are reported as research context, exactly as published. They are not guidance.
Fat mass in diet-induced obese mice
Neelakantan et al. (2018) tested a series of quinolinium-based NNMT inhibitors for membrane permeability, selectivity and mechanism, then treated diet-induced obese mice systemically with 5-amino-1MQ. Later reviews of the paper report lower body weight and white fat mass, smaller adipocytes and lower plasma total cholesterol in treated mice, and secondary summaries report no change in food intake. This is the origin study for the fat-loss claims made about the compound.
- Dose studied
- Systemic treatment for 11 days according to secondary summaries, diet-induced obese mice on a high-fat diet; the mg/kg dose and schedule could not be confirmed from the primary paper
[1] Neelakantan H et al. · 2018 · PMID 29155147 ↗
Glucose, insulin and liver fat in mice
Babula et al. (2024) gave 5-amino-1MQ daily for 28 days to diet-induced obese mice. Treated mice gained less weight and fat mass, showed better glucose tolerance and insulin sensitivity, and had lower circulating insulin. In the liver, steatosis, macrophage infiltration, liver weight and triglyceride levels were all reduced compared with untreated obese mice.
- Dose studied
- Daily dosing for 28 days, diet-induced obese mice; the mg/kg dose and route could not be confirmed for this summary
[4] Babula JJ et al. · 2024 · PMID 39161060 ↗
Combined with a lower-calorie diet in mice
Sampson et al. (2021) switched diet-induced obese mice to a lean diet with or without the NNMT inhibitor. The combination produced greater weight and fat loss than the diet change alone and brought body composition and liver fat measures to the levels seen in age-matched mice kept on the lean diet throughout.
- Dose studied
- NNMT inhibitor (5-amino-1-methylquinolinium) given alongside a switch to a lean diet, diet-induced obese mice; the dose could not be confirmed for this summary
[3] Sampson CM et al. · 2021 · PMID 33707534 ↗
Muscle stem cells in injured aged mice
Neelakantan et al. (2019) injured the tibialis anterior muscle of 24-month-old mice with barium chloride and gave either an NNMT inhibitor (the compound sold as 5-amino-1MQ) or saline. Treatment increased muscle stem cell proliferation and fusion, producing nearly twofold greater muscle fiber cross-sectional area and a shift toward larger fibers compared with controls. In C2C12 mouse muscle cells the inhibitor also enhanced myoblast differentiation.
- Dose studied
- 5 or 10 mg/kg for one week after injury, or 10 mg/kg for three weeks, with saline controls (24-month-old mice)
[2] Neelakantan H et al. · 2019 · PMID 30753815 ↗
Study quality
No human studies of 5-amino-1MQ have been published; all of the evidence comes from mice and cultured cells. The four main studies come from one University of Texas Medical Branch group that designed the compound, so independent replication is lacking. The obesity work uses diet-induced obese mice over short periods (11 to 28 days), with endpoints such as body weight, fat mass, glucose tolerance and liver fat rather than clinical outcomes. The muscle benefit was shown in old mice after a chemical muscle injury, so it says nothing about uninjured muscle. No human pharmacokinetic, dose-finding or safety data exist, and secondary sources that describe human doses derive them from rodent scaling or online reports rather than from any study. Several dose details for the mouse studies could not be confirmed from the primary papers for this summary and are omitted.
References
- 1Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochemical Pharmacology. PMID 29155147
- 2Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochemical Pharmacology. PMID 30753815
- 3
- 4Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunctions. Diabetes, Obesity and Metabolism. PMID 39161060
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