5-Amino-1MQ: What It Is, Capsules vs Vial and Research

5-Amino-1MQ: what it is, capsules vs vial and research

5-amino-1MQ is a small-molecule NNMT inhibitor studied for adipocyte fat storage and NAD+ salvage, with almost entirely preclinical (mouse and cell) evidence. This guide explains what 5-amino-1MQ is, how NNMT inhibition is thought to work, what the research shows and where it stops, how the capsule, vial and pen formats differ, what the iodide salt does to the label mass, and how research-grade material is identified and stored.

What is 5-amino-1MQ?

5-amino-1MQ is the short name for 5-amino-1-methylquinolinium. The core is a quinoline: two fused six-membered rings, one of them containing a nitrogen atom. A methyl group sits on that ring nitrogen and an amino group sits at position 5 of the ring system. Methylating the ring nitrogen leaves it with four bonds and no lone pair, so the molecule carries a positive charge that does not depend on pH. An ordinary amine picks up a proton in acid and gives it back in base; this nitrogen has nothing to give and nothing to take. The charge is structural.

That one fact decides most of its behaviour. The compound dissolves readily in water at any pH and poorly in organic solvents. It cannot exist as a neutral molecule, so what sits in the vial is always a salt, and the counter-ion is part of the mass on the label (more on that below). It crosses lipid membranes poorly compared with molecules that can shed their charge, which matters for any cell-based design.

It is not a peptide. There is no amide backbone, no amino-acid sequence, no oxidisable residue and no conformation to lose. The cation weighs about 159.2 Da, smaller than most dipeptides. It appears in peptide catalogues because the researchers who use it overlap with the researchers who use peptides, not because of any chemical kinship, and the handling advice written for peptides (aliquot on first opening, low-binding tubes, never freeze a solution) exists to slow degradation routes this molecule does not have. Where the peptide boundary sits is covered in a separate guide.

The compound came out of a medicinal chemistry programme at the University of Texas Medical Branch (UTMB) in Galveston, led by Stanley Watowich and Jonathan Hommel, with Harshini Neelakantan as first author on the key papers. Their 2017 structure-activity study in the Journal of Medicinal Chemistry started from 1-methylquinolinium, a weak NNMT inhibitor that resembles the enzyme's product, and tested substituents around the ring. The quinoliniums stood out as a scaffold, with 5-amino-1MQ inhibiting NNMT at an IC50 of about 1 µM, and docking placed the series at the enzyme's nicotinamide binding site. The follow-up paper a year later tested the compound against a panel of structurally similar methyltransferases and two enzymes of the NAD+ salvage pathway, and found no inhibition of DNMT1, PRMT3, NAMPT or SIRT1, and only slight inhibition of COMT at the highest concentrations used. The same group showed the compound crossed membranes in passive and Caco-2 cell assays with no detectable efflux, which is not a given for a permanently charged species, and it became the tool compound for their animal work.

What NNMT does and why inhibiting it is of interest

Nicotinamide N-methyltransferase catalyses a single reaction. It transfers a methyl group from S-adenosylmethionine (SAM) to the ring nitrogen of nicotinamide, producing 1-methylnicotinamide (1-MNA) and S-adenosylhomocysteine (SAH). That is the whole chemistry, and it draws on two separate pools at once.

The first pool is nicotinamide, the main substrate for NAD+ salvage. The enzyme NAMPT converts nicotinamide to nicotinamide mononucleotide, which is then converted to NAD+. Methylating nicotinamide diverts it away from that route and marks it for excretion. The second pool is SAM, the methyl donor for DNA, histone and protein methylation and for polyamine synthesis. Every turn of NNMT consumes one SAM. One enzyme therefore sits at the junction of coenzyme salvage and cellular methylation capacity, which is why it attracted attention in metabolism and cancer biology at about the same time.

The metabolic case was made by Daniel Kraus and colleagues in Barbara Kahn's laboratory, published in Nature in 2014. NNMT expression is higher in the white adipose tissue and liver of obese and diabetic mice. Knocking NNMT down in white adipose tissue and liver with antisense oligonucleotides protected mice from diet-induced obesity by raising cellular energy expenditure. The knockdown raised adipose SAM and NAD+, increased ornithine decarboxylase and SSAT activity by way of an effect on histone H3 lysine 4 methylation in adipose tissue, and raised urinary excretion of diacetylspermine, a direct marker of polyamine flux. Separately, Ulanovskaya and Cravatt reported in 2013 that high NNMT expression in cancer cells creates a methylation sink, draining SAM and lowering histone methylation. Pissios reviewed the field in 2017 under the title "more than a vitamin B3 clearance enzyme".

One qualification belongs here. The product of the reaction, 1-MNA, is not inert. Hong and colleagues reported in Nature Medicine in 2015 that in liver, NNMT and 1-MNA stabilise the deacetylase SIRT1, that suppressing hepatic NNMT alters glucose and cholesterol metabolism, and that adding 1-MNA to a high-fat diet lowered serum and liver cholesterol and liver triglycerides in mice. Inhibiting NNMT changes what is consumed and what is produced, and the two directions do not have to point the same way in every tissue.

How 5-amino-1MQ works: mechanism of action

NNMT methylates a pyridine nitrogen and makes a permanent cation. 5-amino-1MQ is a permanently cationic quinolinium, so it resembles the product of the reaction rather than the substrate, and docking in the 2017 structure-activity study placed this series at the enzyme's nicotinamide binding site. When the enzyme is blocked, less nicotinamide is methylated and less SAM is consumed. In the originating group's cell work with differentiated 3T3-L1 adipocytes, treatment lowered intracellular 1-MNA with a cellular EC50 of 2.3 ± 1.1 µM, raised NAD+ about 1.2- to 1.6-fold over a 1 to 60 µM range, raised SAM, and reduced lipogenesis and lipid droplet accumulation.

That chain (inhibit NNMT, spare nicotinamide, raise NAD+ and SAM, shift adipocyte metabolism away from storage) is the working model. Three points about it deserve plain statement. First, the NAD+ increase comes from sparing a precursor, not from supplying one; 5-amino-1MQ contains no NAD+ and no nicotinamide, so it is a different proposition from the precursors and the injectable NAD+ discussed in the NAD+ guide. Second, the size of any NAD+ effect depends on how much NNMT the tissue expresses, which is high in liver and adipose tissue and much lower elsewhere. Third, a permanently charged molecule needs a way into the cell. Organic cation transporters are the plausible route, and their expression varies between cell types, so uptake should be established in the specific system used rather than assumed.

What the research shows

Diet-induced obesity in mice

The most cited study is Neelakantan et al., Biochemical Pharmacology, 2018. Male C57BL/6 mice were made obese on a high-fat diet over 16 weeks, then treated with 5-amino-1MQ for 11 days while staying on the diet, with nine mice per group. Over those 11 days the saline controls gained 0.6 g, about 1.4 percent of baseline body weight, while treated mice lost 2.0 g, about 5.1 percent. Epididymal white adipose tissue mass fell by about 35 percent, adipocyte size by more than 30 percent, and plasma total cholesterol by about 30 percent. Cumulative food intake did not differ between the groups, 28.1 g against 26.2 g, which argues against a simple appetite effect. The 1-MNA, NAD+ and SAM measurements in that paper were made in cultured adipocytes rather than in the mouse tissue. It is one study, from one group, with a treatment window of under two weeks.

Aged muscle regeneration

The same laboratory reported in 2019 that 5-amino-1MQ, given to 24-month-old mice around a barium chloride injury to the tibialis anterior, increased muscle stem cell proliferation and fusion, produced regenerating fibres with nearly twice the cross-sectional area, and raised peak torque in the injured muscle by about 70 percent against saline controls. NNMT expression rises in aged muscle, and the authors framed the result as lifting a block on stem-cell activation. A 2024 follow-up in Scientific Reports treated mice aged 22 to 24 months with 5-amino-1MQ for eight weeks, with or without progressive weighted wheel running: grip strength rose about 40 percent in treated sedentary mice, about 20 percent in exercised controls, and about 60 percent when the two were combined. Both are small, single-laboratory animal studies.

Evidence from other NNMT tools

Two lines of work support the target without using this compound. Kraus et al. (2014) used antisense knockdown rather than a small molecule and saw protection from diet-induced obesity. Kannt and colleagues at Sanofi (Scientific Reports, 2018) developed a structurally different NNMT inhibitor, JBSNF-000088, and reported reduced body weight, improved insulin sensitivity and glucose tolerance normalised to the level of lean controls in diet-induced obese mice, with none of those effects present in NNMT knockout mice. Agreement across three approaches makes it less likely that the 5-amino-1MQ results are an off-target artefact, though it does not settle the question.

Human data

There is no published, peer-reviewed clinical trial of 5-amino-1MQ. No pharmacokinetic, safety or efficacy data in people have appeared as of this writing. Everything above is mouse or cell culture, and the mouse results have no validated human equivalent. Claims about human fat loss attached to this compound in the marketplace are extrapolations from an 11-day mouse study.

5-Amino-1MQ benefits reported in research models

The word "benefits" needs a frame. Every item below is a finding in mice or cultured cells, reported by the originating laboratory unless stated, and none of it has been tested in a human trial.

• Lower body weight and white adipose mass in diet-induced obese mice over 11 days, with cumulative food intake unchanged (Neelakantan 2018).
• Smaller adipocytes and about 30 percent lower plasma total cholesterol in the same model.
• Higher intracellular NAD+ and SAM, and lower 1-MNA, in cultured adipocytes.
• Reduced lipogenesis and lipid droplet accumulation in differentiated 3T3-L1 adipocytes.
• Activation of muscle stem cells and better regeneration after injury in 24-month-old mice (Neelakantan 2019).
• Gains in grip strength that add to those of weighted wheel running in aged mice (Dimet-Wiley 2024).

Things sometimes attributed to 5-amino-1MQ that the literature does not contain: a human weight-loss result, an effect on appetite, a demonstrated rise in blood NAD+ in people, or any longevity outcome in any species.

What the research has not established

• Anything in humans. No trial, no pharmacokinetics, no safety data. The compound has no approved human or veterinary formulation in any jurisdiction.
• Independent replication of the compound-specific results. The 5-amino-1MQ animal work comes from the UTMB group and its collaborators. Other laboratories have supported NNMT as a target with antisense knockdown and with a structurally different inhibitor, which is helpful but not the same thing, and an unconnected laboratory has yet to publish a full repeat of the compound-specific results.
• Duration. The obesity study ran 11 days, and the longest published course is the eight weeks of the 2024 muscle study. What happens to weight, liver, methylation capacity or 1-MNA-dependent pathways over months of inhibition is unknown.
• Tissue selectivity. NNMT expression varies widely between tissues, and its product has its own biology (the hepatic SIRT1 work above). Whole-body inhibition is a blunt instrument.
• Oral exposure. Every published mouse study cited here used subcutaneous injection. The 2018 paper reported high permeability in membrane and Caco-2 assays (next section), but those are in vitro systems, and no published study has measured absorption of 5-amino-1MQ given by mouth.
• Translation. The mouse results have no validated human equivalent, and allometric scaling of animal amounts is a hypothesis, not data.

Selectivity and membrane permeability

The 2018 paper from the Neelakantan and Watowich group that is usually cited for the obesity result also tested two properties that decide whether a compound is a useful research tool: whether it acts on other enzymes, and whether it can get into cells (Neelakantan et al. 2018). Selectivity was checked against structurally related methyltransferases and against enzymes of the NAD+ salvage pathway, and the methylquinolinium analogues did not inhibit the related SAM-dependent methyltransferases (Neelakantan et al. 2018). That matters because NNMT draws on SAM, the methyl donor it shares with many other methylation reactions (Pissios 2017), so an inhibitor that also blocked other SAM-dependent enzymes would be hard to interpret.

Permeability was measured with a parallel artificial membrane assay and with Caco-2 cell layers. Methylquinolinium scaffolds carrying a primary amine substituent, the group that includes 5-amino-1MQ, showed high permeability through both passive and active transport across membranes (Neelakantan et al. 2018). Those are in vitro assays. They show that the charged quinolinium can cross membranes in those systems, but they are not a measurement of absorption or distribution in an animal, and no study in the references has measured either for 5-amino-1MQ given by mouth. The 2017 docking work, which placed the quinolinium series in the enzyme's nicotinamide-binding site (Neelakantan et al. 2017), gives the structural side of the same selectivity argument.

5-Amino-1MQ capsules vs vial vs pen

PrymaLab lists four formats. They contain the same cation and they suit different questions. The short version from the product pages: the vial is the format for anything quantitative, the capsule is a formulated solid whose fill cannot be inspected, and the pen is a solution whose concentration basis has to come from the certificate.

Two capsule-specific points. A container of sixty units is opened sixty times, or close to it, and every opening admits room air; the fill is hygroscopic and the shells are moisture-sensitive, so a slow failure shows as caking or shells that stick, which is why the desiccant stays in the bottle. Content uniformity is a property of the filling run, so a certificate that reports the spread across several tested capsules is worth more than one that reports a single unit.

One thing that helps with capsules: a declared 50 mg is about 175 micromoles whether the label meant salt or cation, because a mole of salt contains a mole of cation. If a certificate states molar content, the mass ambiguity below disappears. Almost none do.

The iodide salt and what the label mass means

5-amino-1MQ is supplied as the iodide salt, C10H11IN2, formula weight about 286.11, so the stated milligrams include the counter-ion. The cation, which is the species that inhibits the enzyme, weighs about 159.2. Iodide accounts for the remaining 127 or so. That means iodide is roughly 44 percent of the weighed mass and the cation roughly 56 percent, an unusually large counter-ion share, and larger than any counter-ion correction on a peptide in the catalogue.

The arithmetic consequences, stated plainly:

• A nominal 50 mg of iodide salt contains about 28 mg of cation. A nominal 50 mg of cation would be about 90 mg of salt. Those are different articles, and the difference approaches a factor of two.
• A nominal 5 mg of iodide salt contains about 2.8 mg of cation: roughly 17.5 micromoles on a salt basis against 31.4 micromoles if the 5 mg meant free cation.
• A molar concentration calculated from the cation mass against a weight of salt overstates the true value by a factor of nearly 1.8.
• Other salts weigh differently. A chloride salt would come in near 195 g/mol with about 82 percent cation, so two vials both labelled 50 mg could hold substantially different amounts of compound purely from the counter-ion.

The convention in most published work and most supplier documentation is to state mass and concentration on the salt basis, but the convention is not universal and it is not always stated. The check is one question: which salt was supplied, and does the stated mass refer to the salt or the cation. If the answer is not on the certificate, the answer is not known. The same discipline used for net peptide content on peptides applies here; only the arithmetic differs.

Iodide has one more property that is easy to overlook. It is the most easily oxidised of the common halides, which is why these salts discolour. A lot that has darkened has lost some iodide to iodine, which shifts the salt composition slightly and makes the mass basis less reliable than it was on the day of manufacture. Light protection is therefore not a formality for this compound.

What the published studies measured

The table lists what published studies examined, in what model, and what they reported. Where papers give amounts, the basis (salt or cation) is not always stated; Neelakantan et al. 2018 stated theirs on the free-base weight of the cation, which is the exception rather than the rule.

How 5-amino-1MQ is prepared for research use

The compound is a water-soluble salt, so preparation is dissolution rather than reconstitution in the peptide sense. The product pages recommend dissolving a whole 5 mg vial rather than weighing part of it: a balance reading to 0.1 mg gives about two percent error on a 5 mg weighing under good conditions, transfer losses add to that, and volumetric work from a known total is more accurate at this scale. Record the volume, and every later number comes off a pipette rather than a balance.

Two worked examples on the salt basis: 5 mg of iodide salt in 1.0 mL is 5 mg/mL, or about 17.5 mM; 50 mg in 5.0 mL is 10 mg/mL, or about 35 mM. If the certificate states the mass on a cation basis, use 159.2 instead of 286.1 in the molar step.

Solutions keep better than peptide solutions, because there is no backbone to hydrolyse and nothing to aggregate, but a solution should still not sit for weeks unchecked. Make them when needed, keep them cold and protect them from light, since the iodide counter-ion is the light-sensitive part of the salt.

How 5-amino-1MQ should be stored

• Vials (5 mg and 50 mg): -20°C, sealed and dry, protected from light. Bring the vial to room temperature before opening so condensation does not land on cold solid. Reseal between uses; dryness matters for weighing accuracy more than for chemical stability.
• Capsules: sealed, cool, dry and away from light, with the desiccant left in the container. The fill is hygroscopic and the shells are moisture-sensitive; the failure mode is physical (tacky, stuck or distorted shells) rather than chemical.
• Pen: 2-8°C, protected from light, as a ready-filled solution.
• All formats: the compound has no amide bonds, no oxidisable residues and no conformation, so aliquoting on first opening and low-binding consumables are unnecessary. Light protection is the one precaution that does real work, because iodide salts darken as iodide oxidises to iodine.

How to identify research-grade 5-amino-1MQ

A useful certificate of analysis for this compound answers questions a peptide certificate never has to. In order of importance:

1. The salt form, named explicitly, and whether the declared mass refers to the salt or the free cation. These two lines together do the work; either alone leaves half the calculation unknown.
2. Identity of the active by nuclear magnetic resonance or mass spectrometry, run on the fill in the case of capsules rather than on an intact unit.
3. Assay: the quantity found, not the quantity intended, with the method named.
4. Water content, since the article is hygroscopic and containers are opened repeatedly.
5. For capsules, uniformity across several tested units with the spread reported, and a full excipient declaration.
6. Lot number, manufacturing date and the storage condition the figures apply to.

Ideally the certificate also states molar content per unit, which removes the salt ambiguity entirely. Almost no supplier does this, so the salt line and the assay line are the practical minimum.

Where to buy 5-amino-1MQ for research

PrymaLab is a veteran-owned research supplier in Ashland, Kentucky. 5-amino-1MQ is listed with the other metabolic research compounds in the four formats compared above, each with a lot-specific certificate of analysis. Background reading is collected in the Research Hub, ordering questions on the FAQ page, and the company's story on the About PrymaLab page. Everything sold is for research use only.

Frequently asked questions

Key takeaways

• 5-amino-1MQ is a small-molecule NNMT inhibitor, a permanently charged quinolinium cation of about 159 Da. It is not a peptide.
• NNMT consumes nicotinamide and SAM; inhibiting it spares both, which in cultured 3T3-L1 adipocytes raised NAD+ and SAM and reduced lipogenesis.
• The key animal result is an 11-day study in diet-induced obese mice, in which treated mice lost about 5 percent of body weight while controls gained about 1 percent, with about 35 percent less epididymal white adipose mass. There are no human data.
• The compound is supplied as the iodide salt (about 286 g/mol), so a labelled 50 mg holds about 28 mg of cation; the certificate has to state which basis the mass refers to.
• PrymaLab supplies 5 mg and 50 mg vials, 60-capsule bottles and a 3 ml pen for research use; the vial is the format for quantitative work, and all formats are stored dry and away from light.

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References

1. Neelakantan H, Wang HY, Vance V, Hommel JD, McHardy SF, Watowich SJ. Structure-activity relationship for small molecule inhibitors of nicotinamide N-methyltransferase. J Med Chem. 2017;60(12):5015-5028. PubMed
2. Neelakantan H, Vance V, Wetzel MD, Wang HL, McHardy SF, Finnerty CC, Hommel JD, Watowich SJ. 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. PubMed
3. Neelakantan H, Brightwell CR, Graber TG, Maroto R, Wang HL, McHardy SF, Papaconstantinou J, Fry CS, Watowich SJ. 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. PubMed
4. 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. PubMed 38969654
5. Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang YC, Cen Y, Sauve AA, Asara JM, Peroni OD, Monia BP, Bhanot S, Alhonen L, Puigserver P, Kahn BB. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258-262. PubMed
6. Kannt A, Rajagopal S, Kadnur SV, et al. A small molecule inhibitor of nicotinamide N-methyltransferase for the treatment of metabolic disorders. Sci Rep. 2018;8:3660. PubMed
7. Hong S, Moreno-Navarrete JM, Wei X, Kikukawa Y, Tzameli I, Prasad D, Lee Y, Asara JM, Fernandez-Real JM, Maratos-Flier E, Pissios P. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nat Med. 2015;21(8):887-894. PubMed
8. Ulanovskaya OA, Zuhl AM, Cravatt BF. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Nat Chem Biol. 2013;9(5):300-306. PubMed
9. Pissios P. Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends Endocrinol Metab. 2017;28(5):340-353. PubMed
10. PrymaLab. Metabolic research compounds; Research Hub; Peptide calculator; FAQ; About PrymaLab.