Research-use-only context. This article summarizes published third-party scientific literature and laboratory practice. It is not medical advice, not a therapeutic or performance claim, and not a usage guide. US Prime Peptides products are supplied strictly for in vitro laboratory research and are not for human or veterinary use.
This article explains what 5-Amino-1MQ is, why it is a small molecule rather than a peptide, what enzyme it inhibits and why that enzyme attracted attention, and what the published cell-culture and mouse studies report. It sorts the evidence by model system, notes where the literature disagrees with itself, states that no human trial exists, and describes what a certificate for a non-peptide research chemical should show.
5-Amino-1MQ is a quinolinium salt, not a peptide
5-Amino-1MQ is 5-amino-1-methylquinolinium: a quinoline ring system carrying a methyl group on the ring nitrogen, which makes that nitrogen permanently positively charged, and an amino group at carbon 5. The cation has the formula C10H11N2+, a mass of about 159.2 daltons, PubChem CID 950107, and CAS number 685079-15-6. It is supplied as a salt, almost always the iodide, C10H11IN2, molecular weight about 286.1 daltons, PubChem CID 66522933, CAS number 42464-96-0. The literature abbreviates it 5-AMQ, 5MQ, 5A1MQ, or simply NNMTi.
Nothing about this structure is peptide-like. There are no amino acids, no amide backbone, no N- or C-terminus, and no susceptibility to peptidases. The molecule is a flat, aromatic, water-soluble cation that resembles the methylated product of the enzyme it blocks. It appears in research-peptide catalogs because it is handled the same way, as a dry powder reconstituted in water, and is studied in the same metabolic-research context as several peptides. The same is true of two other non-peptides covered on this site, NAD+ and Dihexa. Two handling notes: the iodide counter-ion accounts for about 44 percent of the salt's mass, so the amount of active cation in a labeled mass is well under half, and iodide salts can discolor on light exposure as iodide oxidizes, so amber storage is sensible.
The target enzyme: nicotinamide N-methyltransferase
NNMT is a cytosolic enzyme that transfers a methyl group from S-adenosyl-L-methionine (SAM) to the ring nitrogen of nicotinamide, producing 1-methylnicotinamide (1-MNA) and S-adenosyl-L-homocysteine. Aksoy, Szumlanski, and Weinshilboum cloned the human liver enzyme in a 1994 Journal of Biological Chemistry paper, reporting a 264-residue protein of about 29.6 kilodaltons and noting that NNMT activity in human liver has a bimodal distribution, which suggested a genetic polymorphism. Pissios's 2017 review in Trends in Endocrinology and Metabolism traces how the enzyme went from a vitamin B3 clearance route to a metabolic regulator once it was found at high levels in adipose tissue and in many tumors.
Two consequences of the reaction explain the interest. First, every turnover consumes one nicotinamide, which is the substrate of the NAD+ salvage pathway, so high NNMT activity can divert nicotinamide away from NAD+ synthesis. Second, every turnover consumes one SAM, the universal methyl donor. Ulanovskaya, Zuhl, and Cravatt showed the second effect in a 2013 Nature Chemical Biology paper: in cancer cell lines that overexpress NNMT, the enzyme acted as a methylation sink, draining methyl units from SAM into the stable product 1-MNA, leaving histones and other proteins hypomethylated and shifting gene expression. Riederer and colleagues had earlier reported, in a 2009 Atherosclerosis paper, that 3T3-L1 adipocytes and human and mouse adipose explants express high, enzymatically active NNMT that rises with adipocyte differentiation.
Tissue distribution has been measured directly in mice. Rudolphi and colleagues, in a 2018 Endocrine Research paper, developed a fluorescence assay and found the highest NNMT activity in the white fat beneath the skin, followed by epididymal white fat, with brown fat, liver, and lung several-fold lower and little activity in heart, skeletal muscle, or kidney. Ehebauer, Ghavampour, and Kraus, in a 2020 Life Sciences paper, showed in 3T3-L1 adipocytes that glucose deprivation doubled NNMT mRNA and protein, that blocking glucose transport or glycolysis reproduced the effect, and that AMPK activation or mTOR inhibition did the same, placing NNMT expression under nutrient-sensing control.
The genetic experiments that made NNMT a target
Kraus and colleagues, in a 2014 Nature paper, found Nnmt to be the most strongly reciprocally regulated gene in white adipose tissue when comparing mice with adipose-specific knockout of the Glut4 glucose transporter against mice overexpressing it. NNMT expression was higher in white fat and liver of obese and diabetic mice. Knocking the enzyme down with antisense oligonucleotides in fat and liver protected mice from diet-induced obesity by raising cellular energy expenditure, raised adipose SAM and NAD+ levels, and increased polyamine flux through the enzymes ODC and SSAT, with higher urinary diacetylspermine as a direct readout. That paper is the rationale for every inhibitor program since.
The liver literature complicates the picture. Hong and colleagues, in a 2015 Nature Medicine paper, found that hepatic Nnmt expression is highly variable and correlates with metabolic parameters in mice and humans, that suppressing it in vivo changed glucose and cholesterol handling, and, importantly, that the product 1-MNA itself stabilizes sirtuin 1 protein. Supplying 1-MNA to mice on a high-fat diet lowered serum and liver cholesterol and liver triglycerides. The enzyme's product therefore has activity of its own, and inhibiting the enzyme in liver removes it. The adipose and hepatic findings mean that NNMT inhibition does not act the same way in every tissue, and any model should specify which tissue is being asked about.
How 5-Amino-1MQ was developed and what it does in cells
The compound came from a structure-activity campaign at the University of Texas Medical Branch. Neelakantan and colleagues, in a 2017 Journal of Medicinal Chemistry paper, screened N-methylated quinolinium, isoquinolinium, pyridinium, and benzimidazolium/benzothiazolium analogs against recombinant NNMT and found a greater than thousand-fold activity range, with quinoliniums the most promising scaffold at low-micromolar IC50 values. Docking placed the inhibitors in the nicotinamide-binding site. A companion 2017 Biochemistry paper described the assay: because NNMT methylates quinoline to the fluorescent product 1-methylquinolinium, product formation can be followed in real time without coupled enzymes, and the kinetics fit a random bireactant mechanism.
The 2018 Biochemical Pharmacology paper by Neelakantan and colleagues is the primary characterization of 5-Amino-1MQ as a tool compound. Methylquinoliniums bearing a primary amine showed high permeability in parallel artificial membrane and Caco-2 cell assays, by both passive and active transport, which is not obvious for a permanently charged molecule. The compound did not inhibit structurally related SAM-dependent methyltransferases or the enzymes of the NAD+ salvage pathway. In cultured adipocytes it lowered intracellular 1-MNA, raised intracellular NAD+ and SAM, and suppressed lipogenesis. Akar and colleagues, in a 2021 Journal of Obstetrics and Gynaecology paper, exposed HeLa cervical cancer cells to 0.1 to 500 micromolar 5MQ and measured concentration- and time-dependent loss of proliferation, cell shrinkage and apoptotic bodies, lower phospho-Akt and SIRT1 protein, and changes in TWIST, ZEB1, and SERPIN1 transcripts, while HEK-293 cells were largely unaffected. Those two cell results are the extent of the published in vitro pharmacology.
What the mouse studies report
Four mouse studies form the in vivo literature, all from the same originating group or its collaborators. In the 2018 Biochemical Pharmacology paper, diet-induced obese mice given a potent inhibitor systemically had lower body mass and less white adipose tissue than vehicle controls, with changes in plasma lipids. Neelakantan and colleagues, in a 2019 paper in the same journal, turned to aged skeletal muscle: 24-month-old mice received a barium chloride injury to the tibialis anterior, and animals given the inhibitor for one or three weeks afterward showed more muscle stem cell proliferation, larger regenerating fiber cross-sections, and better in vivo contractile recovery than saline controls. The authors linked this to NNMT overexpression in aging muscle and the NAD+ salvage and SIRT1 axis.
Dimet-Wiley and colleagues, in a 2022 Scientific Reports paper, combined the inhibitor with a switch from a high-fat Western diet to a low-fat diet in diet-induced obese mice and sequenced the cecal microbiome. Mice given the inhibitor plus the diet switch had a distinct microbiome pattern, with lower Erysipelatoclostridium and higher Lactobacillus abundance than diet-switch-only controls, though alpha diversity did not differ between groups. Babula and colleagues, in a 2024 Diabetes, Obesity and Metabolism paper, gave 5A1MQ to diet-induced obese mice for 28 days and measured a concentration-related limiting of body-mass and fat-mass gain, better oral glucose tolerance and insulin sensitivity, lower plasma insulin, less hepatic steatosis and macrophage infiltration, and normalized transaminases and ketone bodies. The same paper established plasma pharmacokinetics in mice and showed distribution into adipose, muscle, and liver.
| Finding | Model | Source |
|---|---|---|
| Quinolinium scaffold, low-micromolar IC50, binds nicotinamide site | Recombinant enzyme, docking | Neelakantan 2017 (J Med Chem) |
| Membrane-permeable; selective over related methyltransferases and salvage enzymes | PAMPA, Caco-2, enzyme panels | Neelakantan 2018 |
| Lower 1-MNA, higher NAD+ and SAM, less lipogenesis | Cultured adipocytes | Neelakantan 2018 |
| Lower body mass and white adipose mass | Diet-induced obese mice | Neelakantan 2018; Babula 2024 |
| More muscle stem cell proliferation after injury | 24-month-old mice | Neelakantan 2019 |
| Distinct cecal microbiome with diet switch | Diet-induced obese mice | Dimet-Wiley 2022 |
| Reduced proliferation, lower SIRT1 and p-Akt | HeLa cells | Akar 2021 |
What is not established, and what a certificate should show
No human trial of 5-Amino-1MQ has been published in the peer-reviewed literature, and the compound is not an approved drug in any jurisdiction. Everything known about its pharmacology in a whole organism comes from mice, and the in vivo work comes from a single academic lineage, so independent replication is still absent. The Hong 2015 finding that the enzyme's product stabilizes SIRT1 in liver has not been reconciled with the inhibitor studies, which report higher SIRT1 signaling in muscle after inhibition; the two tissues may simply behave differently. Off-target activity was tested against related methyltransferases and salvage enzymes, not against a broad receptor or kinase panel.
A certificate for a non-peptide chemical needs different lines, and a buyer should know which to ignore. Identity by LC-MS should show the intact cation at m/z 159.09; there is no multiply charged series and no sequence to confirm. Purity by HPLC with UV detection is meaningful, but a net peptide content line is not, and should be replaced by an assay value in percent by mass that accounts for the iodide counter-ion and any water. The counter-ion should be named, since the iodide and other salts have different molecular weights and therefore different cation content per labeled milligram. Endotoxin and sterility apply only if the lot is filled as a sterile solid. US Prime Peptides lists 5-Amino-1MQ 10 mg, 5-Amino-1MQ 20 mg, and 5-Amino-1MQ 50 mg with lot-matched certificates posted before purchase; the general guide to reading each line is how to read a certificate of analysis.
Frequently Asked Questions
Is 5-Amino-1MQ a peptide?
No. It is 5-amino-1-methylquinolinium, a small aromatic cation of about 159 daltons with no amino acids or peptide bonds, usually supplied as the iodide salt. It sits in research-peptide catalogs because it is handled as a dry powder and studied in the same metabolic-research context as several peptides.
What does 5-Amino-1MQ do?
It inhibits nicotinamide N-methyltransferase (NNMT), the enzyme that methylates nicotinamide using S-adenosylmethionine. In cultured adipocytes it lowered 1-methylnicotinamide, raised NAD+ and SAM, and suppressed lipogenesis; in diet-induced obese mice it limited gain in body mass and fat mass. Those are the published findings, all from cell culture and mice.
Has 5-Amino-1MQ been tested in humans?
No peer-reviewed human trial of 5-Amino-1MQ has been published, and it is not an approved drug anywhere. The in vivo data are limited to mouse studies, nearly all from one academic group, and no independent replication of the mouse results has appeared.
Why is NNMT a target in the first place?
A 2014 Nature paper found NNMT to be the gene most strongly regulated in opposite directions by adipose Glut4 knockout and overexpression, and showed that knocking it down protected mice from diet-induced obesity by raising energy expenditure. A 2013 study also showed the enzyme drains methyl groups from SAM in cancer cells.
Citations
- Aksoy S, Szumlanski CL, Weinshilboum RM. Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization. J Biol Chem. 1994;269:14835-14840. PMID 8182091
- Riederer M, Erwa W, Zimmermann R, Frank S, Zechner R. Adipose tissue as a source of nicotinamide N-methyltransferase and homocysteine. Atherosclerosis. 2009;204:412-417. PMID 18996527
- Ulanovskaya OA, Zuhl AM, Cravatt BF. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Nat Chem Biol. 2013;9:300-306. PMID 23455543
- Kraus D, Yang Q, Kong D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508:258-262. PMID 24717514
- Hong S, Moreno-Navarrete JM, Wei X, et al. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nat Med. 2015;21:887-894. PMID 26168293
- Neelakantan H, Vance V, Wang HL, et al. Noncoupled fluorescent assay for direct real-time monitoring of nicotinamide N-methyltransferase activity. Biochemistry. 2017;56:824-832. PMID 28121423
- Pissios P. Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends Endocrinol Metab. 2017;28:340-353. PMID 28291578
- Neelakantan H, Wang HY, Vance V, et al. Structure-activity relationship for small molecule inhibitors of nicotinamide N-methyltransferase. J Med Chem. 2017;60:5015-5028. PMID 28548833
- Rudolphi B, Zapp B, Kraus NA, et al. Body weight predicts nicotinamide N-methyltransferase activity in mouse fat. Endocr Res. 2018;43:55-63. PMID 29035138
- 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
- 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
- Ehebauer F, Ghavampour S, Kraus D. Glucose availability regulates nicotinamide N-methyltransferase expression in adipocytes. Life Sci. 2020;248:117474. PMID 32112869
- 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;41:1240-1245. PMID 33645410
- 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;12:484. PMID 35013352
- Babula JJ, Bui D, Stevenson HL, et al. Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. Diabetes Obes Metab. 2024;26:5272-5282. PMID 39161060
This article is for laboratory research reference only. US Prime Peptides products are supplied strictly for in vitro research. Not for human consumption.
Related research
Compliance Notice: US Prime Peptides products are supplied strictly for laboratory and academic research purposes only. They are not intended for human or veterinary consumption, diagnosis, treatment, or prevention of any disease. All content on this page is educational in nature and does not constitute medical advice or product claims. Researchers are responsible for handling these compounds in accordance with their institution’s safety protocols and applicable laws.
