5-Amino-1MQ: an enzyme blocker with mouse data and no human trials

A vitamin B3 enzyme that grows with the waistline

In 2014, a Harvard team went looking for the gene that changed most in mouse fat when they deleted or boosted a glucose transporter. The winner was not a famous metabolic switch. It was NNMT, an obscure enzyme best known for helping the body dispose of surplus vitamin B3 ^[1].

When the researchers turned NNMT down in the fat and liver of mice on a high-fat diet, the animals were protected from diet-induced obesity and burned more energy ^[1]. 5-Amino-1MQ is one of the first drug-like molecules built to block the same enzyme.

The appeal: in mice, weight and fat fell without any drop in appetite ^[3]. The catch: everything known about this compound comes from cells and rodents.

From a clearance enzyme to a Texas drug programme

For decades NNMT was filed under "detox". It takes a methyl group from S-adenosylmethionine (SAM), the cell's universal methyl donor, and attaches it to nicotinamide. The product, 1-methylnicotinamide (1-MNA), is eventually excreted ^[11].

Stanley Watowich's group at the University of Texas Medical Branch in Galveston screened families of small charged ring molecules against the enzyme. Methylated quinoliniums stood out, blocking NNMT at around 1 µM, and computer docking placed them in the pocket where nicotinamide normally sits ^[2].

Their 2018 follow-up added amino groups to the quinolinium ring to help the molecules get into cells. Among the candidates, 5-amino-1MQ produced the biggest drop in 1-MNA inside cultured fat cells, so it became the compound tested in obese mice ^[3]. Watowich is the founder of Ridgeline Therapeutics, and several later papers list Ridgeline employees as authors ^[4,5,7].

How it works: plugging a drain

Picture the cell's vitamin B3 supply as a tank that feeds NAD+, the coenzyme every cell needs to turn food into usable energy. NNMT is a drain at the bottom of that tank. Each time it runs, one nicotinamide leaves the NAD+ recycling loop and one methyl group is spent from the SAM pool.

Plug the drain and, in principle, both stay in circulation. In cultured fat cells, 5-amino-1MQ lowered 1-MNA, raised NAD+ about 1.2- to 1.6-fold across a range of concentrations, raised SAM, and cut fat build-up during cell maturation by 50% at 30 µM and 70% at 60 µM ^[3]. Our NAD+ article covers why NAD+ attracts so much research interest.

The compound looked selective, sparing related methyl-transferring enzymes (DNMT1, PRMT3) and the NAD+ enzymes NAMPT and SIRT1 at relevant concentrations ^[3]. In the knockdown mice, less NNMT meant more SAM and NAD+ in fat, faster polyamine turnover and higher energy expenditure ^[1].

What the research shows

The genetic proof of concept (mice)

Kraus and colleagues used antisense drugs to cut NNMT by 60–75% in the fat of mice on a high-fat diet. Compared with controls, the mice had 47% less relative fat mass and 15% more relative lean mass, gained about half as much weight per calorie eaten, and had serum insulin levels roughly 50–60% lower ^[1].

The key 5-amino-1MQ study (mice, n=9 per group)

Male mice made obese on a high-fat diet received injections of 5-amino-1MQ or saline for 11 days ^[3]. Treated mice lost 2.0 g, about 5.1% of their starting weight, while controls gained 0.6 g, about 1.4% ^[3].

Food intake was essentially the same in both groups (26.2 g for treated mice versus 28.1 g for controls over the study), so the weight change was not explained by eating less ^[3].

Epididymal fat mass fell by about 35%, fat cells were more than 30% smaller, and total cholesterol was about 30% lower than in obese controls. The authors reported no observable adverse effects ^[3].

Follow-ups from the same group (mice)

• Diet plus inhibitor: obese mice switched to a lean diet lost 2.9 g on the diet alone and 6.3 g when the NNMT inhibitor was added. Fat mass fell about 29% versus 3% ^[4].
• Metabolic health: in a 28-day study, 5-amino-1MQ limited weight and fat gain in a dose-dependent way, improved glucose tolerance and insulin sensitivity, and reduced fatty liver changes ^[5].
• Ageing muscle: in 24-month-old mice with injured leg muscle, an NNMT inhibitor from the same programme produced regenerating fibres nearly twice as large and about 70% more peak force ^[6]. In 22- to 24-month-old mice, eight weeks of 5-amino-1MQ raised grip strength about 40%, versus 20% for exercise alone and 60% for both together ^[7].

Human evidence: about the enzyme, not the drug

In 199 surgery patients, people with type 2 diabetes had higher NNMT expression in their fat, and blood 1-MNA tracked insulin resistance. In two further groups (60 people on an exercise programme, 55 bariatric surgery patients), interventions that improved insulin sensitivity lowered fat NNMT ^[8]. That is an association. It does not show that blocking NNMT helps people.

What we don't know yet

• Any human result. No human safety or efficacy data exist. Our guide to levels of evidence explains why mouse results often fail to carry over.
• Independent replication. Almost all in vivo 5-amino-1MQ data come from one research group, and later papers declare links to the company it founded ^[4,5,7].
• Whether less NNMT is always better. In NNMT knockout mice, effects depended on sex and diet: males on a high-fat diet gained insulin sensitivity but not better glucose tolerance, while weight effects appeared in females on a Western diet ^[9].
• The liver. In mice, liver NNMT and its product 1-MNA had metabolic benefits: adding 1-MNA to a high-fat diet lowered cholesterol and liver fat, through the protein SIRT1 ^[10]. That points the opposite way.
• Conflicting human signals. In a human weight-loss study, NNMT in fat biopsies rose while blood 1-MNA fell ^[9].
• Safety. Studies lasted 11 days to 8 weeks. At the highest concentration tested (600 µM) the compound killed about 40% of cultured fat precursor cells ^[3], and no long-term toxicology has been published. NNMT also helps clear excess vitamin B3 and shapes the cell's methyl supply, so chronic blockade could have effects nobody has measured ^[11].
• Small, narrow samples. The 2018 study used nine male mice per group ^[3].

Regulatory status

• Approval: 5-Amino-1MQ is not approved as a medicine by the FDA, the EMA or any other regulator, and has no registered human trials (our ClinicalTrials.gov check, October 2026).
• US compounding: it does not appear on the FDA's list of bulk substances flagged for significant safety risks in compounding (version current as of April 2026) ^[14].
• Sport: it is not named on the 2026 WADA Prohibited List. The S0 class, however, bans at all times any pharmacological substance with no current approval for human therapeutic use, a description this compound appears to fit ^[12].

In the lab: handling and storage

Unlike the peptides in our catalogue, the 5-Amino-1MQ research compound is a small organic salt, typically supplied as a dry solid; the iodide form has a molecular weight of 286.11 g/mol, against 159.21 for the active cation ^[13]. Common practice is long-term storage at −20 °C, sealed, dry and protected from light, with 2–8 °C acceptable for short periods. No published data cover its stability in solution, so laboratories usually prepare solutions fresh or freeze single-use aliquots to avoid repeated freeze–thaw cycles. Our storage guide covers the general principles.

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