5-Amino-1MQ 10mg (5-amino-1-methylquinolinium)

5-Amino-1MQ is not a peptide. It is 5-amino-1-methylquinolinium, a small synthetic organic cation of 159.21 g/mol built on a quinoline ring whose nitrogen carries a permanent methyl group. It contains no amino acids and no peptide bonds. It is stocked and discussed alongside peptides because the research audience overlaps, not because the chemistry does, and that single misunderstanding is the source of most of the incorrect information circulating about it.

The molecule exists for one purpose: to occupy the nicotinamide-binding pocket of nicotinamide N-methyltransferase (NNMT, EC 2.1.1.1) and stop the enzyme working. It came out of a structure-guided screen of N-methylated quinolinium, isoquinolinium, pyridinium and benzimidazolium analogues reported by Neelakantan and colleagues in the Journal of Medicinal Chemistry in 2017, where the quinolinium scaffold emerged as the most tractable and 5-amino substitution gave an IC50 near 1 µM against the human enzyme.

Everything published about its effects comes from cell culture and from mice. As of August 2026 there is no registered clinical trial of 5-Amino-1MQ or of any other NNMT inhibitor on ClinicalTrials.gov, no published Phase 1 pharmacokinetic study, and no human safety dataset of any kind. The preclinical record is genuinely interesting and internally consistent across four independent laboratories. It is also entirely preclinical, and this page is written on that basis.

NNMT is a cytosolic methyltransferase that takes a methyl group from S-adenosylmethionine (SAM) and attaches it to nicotinamide, producing 1-methylnicotinamide (1-MNA) and S-adenosylhomocysteine. Nicotinamide is the salvage-pathway precursor for NAD+, so every molecule the enzyme methylates is a molecule that cannot re-enter NAD+ synthesis. Methylation is a one-way exit: mammals have no enzyme that converts 1-MNA back to nicotinamide. NNMT therefore acts as a drain on two currencies at once, the NAD+ pool and the cellular SAM pool.

In white adipose tissue that drain becomes large in obesity. Kraus and colleagues showed in Nature in 2014 that Nnmt is the most strongly reciprocally regulated gene in adipose tissue between Glut4-knockout and Glut4-overexpressing mice, and that NNMT expression rises in white adipose tissue and liver of obese and diabetic mice. Kannt and colleagues then found the same pattern in people: patients with type 2 diabetes carried roughly twofold higher NNMT mRNA in both omental and subcutaneous white adipose tissue than controls, and plasma 1-MNA tracked both tissue NNMT expression and the degree of insulin resistance across 199 surgical patients.

5-Amino-1MQ is a substrate-site competitive inhibitor: it mimics the nicotinamide the enzyme expects and blocks it. In differentiated 3T3-L1 adipocytes, 24 hours of treatment cut intracellular 1-MNA in a concentration-dependent fashion across 0.3 to 60 µM, raised intracellular NAD+ by roughly 1.2 to 1.6 fold, and raised SAM significantly at 30 µM. The consequence Kraus proposed for the SAM half of the story is polyamine flux: more SAM means more substrate for ornithine decarboxylase and spermidine-spermine N1-acetyltransferase, and the futile polyamine synthesis and catabolism cycle those enzymes drive consumes ATP, raising oxygen consumption in adipocytes without any change in food intake.

A peptide is a chain of amino acids joined by amide bonds, assembled by solid-phase synthesis, characterised by sequence, and quantified with a net peptide content figure that accounts for counter-ions and residual water. None of that applies here. 5-Amino-1MQ is a single fused bicyclic aromatic ring system: quinoline, methylated at the ring nitrogen and carrying a primary amine at the 5-position. There is no sequence to report, no net peptide content to correct for, and no amino acid analysis that would mean anything.

The methylation at the ring nitrogen is what makes the molecule what it is. A neutral quinoline nitrogen can gain or lose a proton with pH. A quaternised one cannot: the nitrogen holds four bonds and a formal positive charge permanently, at every physiological pH. That is why PubChem records the compound as C10H11N2+ rather than a neutral formula, and why it is supplied as a salt with a counter-ion, usually iodide, rather than as a free base. A permanently charged organic cation is a real pharmacological category with its own behaviour, and the whole oral-availability discussion around this compound descends from it.

The practical consequence for anyone reading a certificate of analysis is that mass accounting differs. A 10 mg quantity of the iodide salt at 286.11 g/mol contains roughly 5.6 mg of the 159.21 g/mol active cation, the iodide making up the balance. A COA that reports purity by HPLC area percent says nothing about which of those two masses the label refers to. Vendor pages routinely list the cation formula and the salt mass together, or neither, and no two agree.

The target was validated genetically before any inhibitor existed. Kraus and colleagues knocked NNMT down in white adipose tissue and liver of mice using an antisense oligonucleotide and reported in Nature in 2014 that the animals were protected against diet-induced obesity, glucose intolerance and hepatic steatosis, with the protection driven by increased cellular energy expenditure rather than reduced food intake. Adipose SAM and NAD+ both rose, ornithine decarboxylase and spermidine-spermine N1-acetyltransferase activity and expression both increased, and urinary diacetylspermine excretion rose, giving direct evidence of the polyamine flux the authors proposed as the mechanism. Adipocyte oxygen consumption increased in a manner dependent on those same enzymes.

The human observational layer arrived the following year. Kannt and colleagues measured NNMT mRNA in omental and subcutaneous white adipose tissue across three cohorts: 199 patients undergoing abdominal surgery, 60 individuals on a 12-week exercise programme, and 55 patients in a two-step bariatric surgery programme. Type 2 diabetes was associated with roughly twofold higher NNMT expression in both depots, and plasma 1-MNA correlated with both tissue NNMT expression and the degree of insulin resistance. That work established 1-MNA as a candidate circulating biomarker of NNMT activity, which is exactly what the later mouse studies used to demonstrate target engagement.

A second chemotype confirmed the pharmacology independently. Kannt and colleagues reported JBSNF-000088, a 6-methoxynicotinamide analogue with an entirely different scaffold, in Scientific Reports in 2018. At 50 mg/kg twice daily by oral gavage for 4 weeks in C57BL/6N mice on a 60% kcal fat diet, n = 8 to 10 per group, it reduced body weight against vehicle with comparable food intake, normalised oral glucose tolerance to lean control levels by day 28, improved HOMA-IR, and cut plasma 1-MNA by roughly half. In ob/ob and db/db mice the same compound improved glucose tolerance with no weight difference at all, which is a useful reminder that the metabolic and the body-composition effects of NNMT inhibition are separable.

The founding in vivo experiment is short and specific. Neelakantan and colleagues fed C57BL/6 mice a 45% kcal fat diet for 16 weeks to roughly 38 g body weight, then randomised them into balanced cohorts of nine. Treated animals received 20 mg/kg 5-Amino-1MQ subcutaneously at three fixed times a day for 11 days; controls received saline on the same schedule. Body weight diverged progressively, epididymal fat pad mass fell roughly 35%, adipocyte size fell more than 30%, total plasma cholesterol fell roughly 30% to levels the strain vendor reports for age-matched chow-fed animals, and cumulative food intake was statistically indistinguishable between groups. Triglycerides were excluded because the samples haemolysed.

Sampson and colleagues asked the more useful question of whether the compound adds anything to a diet change. 22-week-old diet-induced obese mice were switched from a 60% kcal fat diet to a 45% kcal Western diet and given the inhibitor daily by intraperitoneal injection for 7 weeks. Diet switch alone produced a 2.9 g fall in body weight and a 2.9% reduction in fat mass. Diet switch with the inhibitor produced 6.3 g and a 29.3% fat mass reduction, normalising body composition to age-matched lean-diet controls and reducing liver adiposity by more than 45%. A companion study from the same group found the combination established a distinct caecal microbiome relative to either intervention alone.

Babula and colleagues ran the longest and most carefully instrumented version in 2024, at 10 and 32 mg/kg/day subcutaneously for 30 days with n = 8 per group. The design tested prevention of gain rather than reversal of established mass: control and low-dose animals added 4.7 g of fat mass over the study while the high-dose group added little. Fed-state insulin rose 112% in controls and fell 9% at the high dose. Crucially the authors adjusted the glucose tolerance result for both body weight and fat mass as covariates and the treatment effect survived, and lean mass was unaffected across all groups.

The muscle work is the part of the literature that is least represented on product pages and is arguably the more surprising result. NNMT is overexpressed in aged skeletal muscle, and the same NAD+ salvage impairment that the adipose story turns on has been linked to sirtuin 1 dysregulation and muscle stem cell senescence. Neelakantan and colleagues tested that in 2019 by injuring the tibialis anterior of 24-month-old mice with barium chloride and treating with 5 or 10 mg/kg inhibitor for one week or three weeks after injury, tracking muscle stem cell activity with systemic 5-ethynyl-2'-deoxyuridine.

Muscle stem cell proliferation and subsequent fusion were both elevated in treated animals. Regenerating myofiber cross-sectional area reached close to twice that of controls, with the fiber size distribution shifted toward larger fibers, and three weeks of treatment produced larger fibers than one week. Contractile function followed the histology: peak tibialis anterior torque was roughly 70% higher than in saline controls. C2C12 myoblast cultures reproduced the differentiation effect in vitro with corresponding shifts in NAD+/NADH ratio.

Dimet-Wiley and colleagues extended this to uninjured aged muscle in 2024, treating mice from 22 to 24 months of age with the inhibitor, an intensive exercise protocol, or both. Sedentary treated animals gained roughly 40% grip strength against sedentary controls; exercise alone gave roughly 20%; the combination gave roughly 60%, so the two interventions were additive rather than redundant. Intramyocellular lipid content improved with treatment, and gastrocnemius fiber cross-sectional area increased significantly only in the combination arm. Proteome and metabolome profiling found the combination engaged molecular processes distinct from either single intervention, which is unusual and is the reason the finding is worth tracking.

For years the only pharmacokinetic statement available was that the methylquinolinium scaffold looked promising. Neelakantan and colleagues measured permeability rather than exposure: in a parallel artificial membrane permeability assay 5-Amino-1MQ showed passive permeability of 3.01 x 10-6 cm/s where both 1-methylquinolinium and 1-MNA showed none, and in a bidirectional Caco-2 monolayer assay it crossed readily with an efflux ratio of 1.33, meaning no meaningful active export. Those are membrane numbers, not bioavailability numbers, and the 2018 paper explicitly closed by naming an improved ADME profile as future work.

The exposure data arrived in 2024 and it is unambiguous. In adult male C57Bl/6J mice, 30 mg/kg by oral gavage produced a Cmax of 14.5 ng/mL at a delayed Tmax of 4 hours and an AUC of 224 ng*h/mL, giving an oral bioavailability of 3.5%. The same molecule given subcutaneously at 25 mg/kg reached a Cmax of 7,010 ng/mL within about 15 minutes with an AUC of 7,031 ng*h/mL and a terminal half-life of 13.3 hours, falling to 12.8 hours on repeated once-daily dosing. Intravenous dosing at 5 mg/kg gave a plasma clearance of 101 mL/min/kg, a steady-state volume of distribution of 39 L/kg and a terminal half-life of 6.3 hours.

The 3.5% figure is not a solubility problem. The compound dissolves above 100 mg/mL in phosphate-buffered saline and above 10 mg/mL in simulated gastric fluid, and binds mouse plasma protein at only 7%. The authors attribute the loss to limited enteric absorption plus high hepatic first-pass metabolism, and their compartmental modelling of the oral data supports rapid hepatic elimination specifically. Limited enteric absorption is the expected behaviour of a permanently charged quaternary cation faced with an intestinal epithelium, and it is why the same paper names species-specific high metabolic clearance as an open optimisation problem.

Two further facts belong on the record because they are absent from essentially every other page about this compound. Following repeated subcutaneous dosing to steady state, drug exposure in epididymal white adipose tissue and quadriceps peaked at 1 hour and declined between 4 and 8 hours, with 1-MNA in those tissues moving inversely, so target engagement is real but brief within each dosing interval. And in a Cerep screen against a broad panel of receptors, enzymes and uptake transporters at 10 µM, the only significant off-target hit was 67.4% inhibition of human monoamine oxidase A. The authors raise the possibility that part of the glucose tolerance benefit is MAO-A mediated rather than NNMT mediated, and list removing that activity as an objective for the next analogue.

No brain distribution data has been published for 5-Amino-1MQ, and no pharmacokinetic parameter of any kind has been measured in a human, a dog or a non-human primate. Half-life figures of 3.8 to 6.9 hours, 5 to 8 hours and 12 to 16 hours all circulate online, sometimes attributed to studies that do not exist. The only measured half-lives are the mouse values above.

5-Amino-1MQ and NAD+ are both discussed as ways to raise cellular NAD+, and they sit at opposite ends of the same pathway. NAD+, and precursors such as nicotinamide riboside and nicotinamide mononucleotide, add substrate: more raw material enters the salvage pathway and, if the salvage enzymes have capacity, more NAD+ comes out. 5-Amino-1MQ removes a competing sink: it blocks the reaction that diverts nicotinamide away from salvage. One pushes on the supply side, the other closes a drain.

The difference that matters experimentally is tissue selectivity. Supplying a precursor raises NAD+ wherever the salvage machinery is active, which is nearly everywhere. Inhibiting NNMT can only matter where NNMT activity is high enough to be limiting, which in the published work means liver, white adipose tissue and aged skeletal muscle. That is a narrower and more targeted intervention, and it is also why NNMT inhibition should not be described as a general NAD+ booster. The observed increase in cultured adipocytes was 1.2 to 1.6 fold, not an order of magnitude.

There is also a second currency involved that precursor supplementation does not touch. NNMT consumes SAM as its methyl donor, so inhibiting it raises SAM as well as NAD+. The polyamine flux and histone H3 lysine 4 methylation changes Kraus reported in adipose tissue follow from the SAM arm, not the NAD+ arm. Anyone modelling NNMT inhibition purely as an NAD+ intervention is describing half of it.

No study has run the two head to head. There is no published experiment comparing 5-Amino-1MQ against NAD+, nicotinamide riboside or nicotinamide mononucleotide in a matched model, and no published data on combining them in any species. Both are stocked here as separate research materials, and any relationship between them in an experimental design is currently a hypothesis rather than a finding.

Because this is a small molecule rather than a peptide, the analytical conventions differ. The quinolinium ring is a strong chromophore, so reversed-phase HPLC with UV detection at the compound's absorption maximum is straightforward, and the original permeability work quantified donor and acceptor well concentrations spectrophotometrically against calibration curves spanning 400 to 3.125 µM. Every published quantification in biological matrix, by contrast, used LC-MS/MS, because plasma and tissue concentrations sit in the low ng/mL range and because 1-MNA has to be measured alongside the parent compound to demonstrate target engagement.

The permanent positive charge affects chromatography. A quaternary cation is poorly retained on a plain C18 column in a simple aqueous-organic gradient and typically needs an ion-pairing reagent or a HILIC stationary phase to elute as a usable peak. A certificate of analysis that reports a single sharp peak at high area percent without specifying the mobile phase system is less informative than the same document would be for a peptide, where a standard gradient is understood.

Identity confirmation should name the salt. A mass spectrum of the cation gives m/z 159 for C10H11N2+, while the iodide salt has a formula mass of 286.11 g/mol. A document that reports 159.21 g/mol for material supplied as the iodide, without saying so, has understated the mass in the vial by nearly half. Widely circulated figures of C10H12N2O and 173.21 g/mol correspond to neither species and appear to be a transcription error propagated between catalogue listings; one commonly quoted CAS number, 1005-39-6, belongs to 2-methylsulfanylpyrimidine-4,6-diamine, an unrelated compound.

Handling follows ordinary small-molecule practice rather than peptide practice. The compound is very soluble in aqueous buffer, above 100 mg/mL in phosphate-buffered saline, and the published mouse work prepared solutions weekly in sterile saline, filtered through a 0.2 µm membrane and stored at 4 degrees C. Lyophilised material is stored frozen and protected from light and moisture; aromatic amines are prone to oxidative discolouration, and quaternary ammonium iodides can be hygroscopic, so a stock that has darkened or deliquesced should be re-assayed before use rather than assumed intact.

There is no human data of any kind. No Phase 1, no pharmacokinetic study, no tolerability cohort, no case series. A search of ClinicalTrials.gov in August 2026 returns no registered study of 5-Amino-1MQ, and none for any other NNMT inhibitor as an intervention. The compound has no regulatory authorisation in any jurisdiction and is not the subject of a published investigational new drug application.

Chronic toxicology is also missing. The longest published in vivo exposure is 7 weeks, in mice. The 2018 study reported no overt toxicity or adverse behavioural signs across 11 days and the 2024 study reported normalised liver enzymes rather than raised ones, but neither is a toxicology programme, and no repeat-dose study in a second species has been published. The MAO-A activity identified in the 2024 off-target screen has not been characterised further in vivo.

Two specific gaps are worth naming because they bear directly on how the preclinical findings should be read. First, the adipose and muscle results come predominantly from one research group across a series of related papers, with independent confirmation of the target coming from a different chemotype rather than from an independent replication of 5-Amino-1MQ itself. Second, allometric scaling from a mouse subcutaneous dose is not a human-equivalent dose, and the pharmacokinetics that would be needed to attempt such a conversion have never been measured in any species other than mouse.