5-amino-1MQ: what the NNMT inhibitor does and where the evidence ends

5-amino-1MQ has promising mouse data and no human data. It is a small molecule that inhibits the enzyme NNMT, and every efficacy result published so far comes from cells and rodents. If a patient asks about it, that is the answer.

Key points

• 5-amino-1MQ is not a peptide. It is a methylated quinolinium cation that inhibits nicotinamide N-methyltransferase (NNMT), with an IC50 of about 1 µM in its chemical series [4][5].
• Suppressing NNMT in adipose tissue and liver protected mice against diet-induced obesity and raised adipose NAD⁺ and SAM [1].
• In obese mice, 5-amino-1MQ was associated with lower body weight and white fat mass, with no change in food intake [5][7].
• In 24-month-old mice, NNMT inhibition was associated with greater muscle regeneration and roughly 70% higher peak torque after injury [8].
• The evidence ends at rodents. There are no human trials published in PubMed or registered on ClinicalTrials.gov [13].

US status (October 2026): See the peptide status tracker.

5-amino-1MQ is a small molecule sold as a peptide

5-amino-1MQ has no peptide bonds. It is 5-amino-1-methylquinolinium, a low-molecular-weight aromatic cation from a series of NNMT inhibitors characterized in 2017 by a group at the University of Texas Medical Branch in Galveston. In that series, methylated quinoliniums inhibited the enzyme with an IC50 of about 1 µM and, according to molecular docking, would bind selectively to the nicotinamide site [4]. It shows up on peptide menus because it reaches the same audience interested in metabolism and longevity. Before you take any vendor’s label at face value, read how to vet a peptide supplier.

NNMT sits between NAD⁺ and methylation

NNMT methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as the methyl donor. That links two systems: the nicotinamide pool the cell would use to regenerate NAD⁺, and the methyl-group balance that regulates, among other things, histone methylation [1][2]. A highly active NNMT, in theory, diverts NAD⁺ precursors and consumes SAM.

The work that put the enzyme on the map was Kraus and colleagues in Nature (2014). NNMT expression was increased in white adipose tissue and liver of obese and diabetic mice. Knocking it down in those tissues protected against diet-induced obesity by increasing cellular energy expenditure. Inhibition raised adipose NAD⁺ and SAM. The authors concluded that NNMT is “a unique and attractive target for treating obesity and type 2 diabetes” [1].

The signal has an observational human correlate. In 199 patients undergoing abdominal surgery, adipose NNMT expression was roughly twofold higher in those with type 2 diabetes and correlated with insulin resistance. Exercise and bariatric surgery were associated with a significant reduction in that expression [3]. This is an association. It does not show that inhibiting the enzyme benefits people.

In obese mice, 5-amino-1MQ reduced fat without reducing food intake

In 2018 the same group tested the compound in adipocytes and mice. In culture, the inhibitors reduced the enzyme’s product (1-methylnicotinamide), raised intracellular NAD⁺ and SAM and suppressed lipogenesis. 5-amino-1MQ did not inhibit related methyltransferases or NAD⁺ salvage enzymes [5]. In male mice with diet-induced obesity, treated subcutaneously for 11 days, it was associated with a significant reduction in body weight and white fat mass, smaller adipocytes and lower total cholesterol, with no change in food intake and no observable adverse effects [5].

Later studies widened the picture. Combined with a switch to a lean diet, an NNMT inhibitor normalized body composition and liver adiposity to the levels of lean control mice, better than diet alone [6]. In 2024, 28 days of 5-amino-1MQ in obese mice dose-dependently limited weight and fat gain, improved oral glucose tolerance and insulin sensitivity, attenuated hepatic steatosis and normalized transaminases [7].

• About 70%: higher peak torque of injured muscle in treated old mice [8]
• 38.4%: oral bioavailability of 5-amino-1MQ in rats [10]
• 0: human trials registered on ClinicalTrials.gov [13]

In aged mice, NNMT inhibition improved muscle repair and strength

NNMT rises with age in skeletal muscle. In 24-month-old mice with an acute tibialis anterior injury, the inhibitor (5 and 10 mg/kg) increased muscle stem cell proliferation and fusion, with nearly 2-fold greater fiber cross-sectional area and roughly 70% higher peak torque than controls [8]. In mice treated from 22 to 24 months of age, grip strength was about 40% greater than in sedentary controls, versus 20% with exercise alone and 60% with both combined [9].

An independent group reported a consistent result in 2025. In mice with hindlimb ischemia (n = 24), NNMT inhibition improved strength (p < 0.0001), power and total work of the ischemic muscle without changing perfusion. In the same study, NNMT was elevated in muscle from patients with peripheral artery disease [11].

The longevity interest runs through NAD⁺

The longevity field’s interest comes from the NAD⁺ pathway. Rather than supplying precursors, NNMT inhibition aims to have the cell divert less nicotinamide, with NAD⁺ increases seen in mouse adipocytes and adipose tissue [1][5]. In 2026, a kidney study linked NNMT to tubular senescence and fibrosis in human biopsies, and selective inhibition of the enzyme was protective in cells, organoids and mice [12]. For the broader picture of NAD⁺, MOTS-c and other longevity molecules, see Epitalon, MOTS-c, NAD+ and SS-31 and the NAD+ status page.

The evidence ends at rodents

Everything above comes from cells and rodents. A ClinicalTrials.gov search returns no registered study of 5-amino-1MQ, and PubMed contains no human trials [13]. The published pharmacokinetic data are from rats: oral bioavailability of 38.4% and terminal half-life of 3.80 h intravenously and 6.90 h orally [10]. No half-life, effective dose or safety profile has been established in humans.

• Short duration. Efficacy studies last from 11 to 28 days or a few weeks, mostly in male mice [5][7][8].
• One dominant group. Most 5-amino-1MQ work comes from the Watowich and Neelakantan laboratory. Several papers disclose that the founder and employees belong to Ridgeline Therapeutics, which develops NNMT inhibitors [6][7][9].
• Double-edged biology. NNMT has beneficial roles in the liver and its role varies by tissue, so blocking it systemically is not a neutral effect by definition [2].
• The human link is correlational. Elevated NNMT in adipose tissue of people with diabetes does not show that inhibiting it improves clinical outcomes [3].

What this means for you

5-amino-1MQ is a well-characterized laboratory tool: documented selectivity against other methyltransferases, a validated method to measure it in plasma and known pharmacokinetics in rats [5][10]. None of that is a human dose, a human half-life or a human safety profile [13]. Products marketed for “research use only” are not a lawful route to patients; see research-use-only peptides. For metabolic patients, start from therapies with human outcome data through a weight management program.

References

1. Kraus D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258-62. PMID 24717514. Link
2. Roberti A, et al. Nicotinamide N-methyltransferase: at the crossroads between cellular metabolism and epigenetic regulation. Mol Metab. 2021;45:101165. PMID 33453420. Link
3. Kannt A, et al. Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance. Diabetologia. 2015;58(4):799-808. PMID 25596852. Link
4. Neelakantan H, et al. Structure-activity relationship for small molecule inhibitors of nicotinamide N-methyltransferase. J Med Chem. 2017;60(12):5015-5028. PMID 28548833. Link
5. Neelakantan H, 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. Link
6. Sampson CM, 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. Link
7. Babula JJ, et al. Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. Diabetes Obes Metab. 2024;26(11):5272-5282. PMID 39161060. Link
8. Neelakantan H, 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. Link
9. Dimet-Wiley AL, 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. Link
10. Awosemo O, et al. Development & validation of LC-MS/MS assay for 5-amino-1-methyl quinolinium in rat plasma: application to pharmacokinetic and oral bioavailability studies. J Pharm Biomed Anal. 2021;204:114255. PMID 34304009. Link
11. Dong G, et al. Nicotinamide N-methyltransferase inhibition improves limb function in experimental peripheral artery disease. Physiol Rep. 2025;13(20):e70615. PMID 41108586. Link
12. Chanvillard L, et al. NNMT inhibition counteracts tubular senescence and fibrosis in early stages of chronic kidney disease. Cell Rep. 2026;45(1):116823. PMID 41543936. Link
13. ClinicalTrials.gov. API v2 search: “5-amino-1MQ” and “5-amino-1-methylquinolinium” (0 registered studies); supplementary PubMed search with no human trials. Accessed October 9, 2026. Link

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