5-Amino-1MQ

NNMT inhibitor

5-Amino-1MQ (NNMT inhibitor) is a metabolic & fat loss research compound. Inhibits NNMT, sparing NAD+ and SAM and shifting fat cells toward energy expenditure.

How 5-Amino-1MQ works

Inhibits NNMT, sparing NAD+ and SAM and shifting fat cells toward energy expenditure.

Proposed benefits

Researched for fat oxidation, appetite and energy regulation, insulin sensitivity and endurance capacity.

Where to get 5-Amino-1MQ

5-Amino-1MQ is sold in 3 forms. They are not interchangeable — the dose and the route differ, so pick the one this page describes unless you know why you want another.

The evidence for 5-Amino-1MQ

Graded by what exists behind each claim.

Human clinical evidence

• No randomized human trials — a research compound with no commercial route to funding one, so the correlative and theoretical tiers are the evidence base rather than a consolation prize.

📊 Correlative data

• No published human series. Reported use is for fat loss and energy, and the consistent theme in the anecdotal record is that it is subtle — which is at least consistent with a mechanism that shifts NAD+ salvage rather than suppressing appetite.
• Beyond that the record is self-reported: community dosing logs are real information about tolerability and almost none about efficacy.

🧪 How the mechanism reads

• An NNMT inhibitor. NNMT consumes methyl groups and degrades nicotinamide, so inhibiting it is predicted to raise cellular NAD+ and free up methyl donors — a fundamentally different route to NAD+ than supplying a precursor like NMN or NR.
• Mouse work shows reduced fat mass and reversal of diet-induced obesity without appetite change. NNMT is highly expressed in white adipose tissue, which is the mechanistic argument that the effect should be relatively fat-selective — and the reason the same logic does not obviously extend to lean subjects.

Why an empty tier is not a verdict → · What community dosing logs are worth →

How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →

What 5-Amino-1MQ actually does

NNMT does one chemical thing: it takes a methyl group off S-adenosylmethionine and puts it onto nicotinamide. Two products come out — methylnicotinamide, and S-adenosylhomocysteine.

Both halves of that sentence matter, and the second half is the one nobody selling this compound mentions. Nicotinamide is the salvage substrate your cells use to rebuild NAD+; methylating it takes it out of the pool permanently, so NNMT is a drain on NAD+ that works by disposal rather than by consumption. That is a genuinely different route from NMN or NR, which add precursor to the front of the same pathway. One turns the tap up. This one plugs the drain.

The other product, S-adenosylhomocysteine, hydrolyzes to homocysteine. So NNMT activity spends methyl groups and generates homocysteine as a by-product, and inhibiting it should do the reverse of both. Hold onto that — it is the only thing on this page you can settle with a blood draw.

Cell, rodent, human — and where it stops

In cells. Silencing NNMT in colon cancer cells raised NAD+ by about 30%; overexpressing it dropped NAD+ by about the same, which is as clean a demonstration of the mechanism as this field has. Reported in the 2024 review, Sun 2024.

In rodents. Kraus 2014 knocked NNMT down in white adipose tissue and liver with an antisense oligonucleotide, in mice on a high-fat diet. The animals were protected from diet-induced obesity — roughly 47% less relative adiposity by the 2024 review's reading — and the mechanism was not appetite. NNMT inhibition raised adipose SAM and NAD+, upregulated ODC and SSAT, and the animals excreted more diacetylspermine in urine. That is a futile polyamine cycle: the cell spends ATP building and dismantling polyamines, and the energy goes out as heat. Adipocyte oxygen consumption went up. Brachs 2019 reproduced the weight and adiposity effect in female mice on a Western diet; Hong 2015 saw fasting glucose fall.

The obstacle. Every step above is a knockdown of the gene, not a drug given by mouth, and the readout that explains the effect — polyamine flux — has never been measured in a human taking an NNMT inhibitor. As of the 2024 review, no NNMT inhibitor of any kind has entered a human trial. Not this one, not JBSNF-000088, not any of the dual-substrate series. So the honest shape of the evidence is: the enzyme chemistry is settled, the rodent phenotype is real and reproduced, and the entire translation step is empty.

5-Amino-1MQ pharmacokinetics — how much of it actually gets in

The card reads “Short (~hours; not fully characterized)” and the tilde is carrying the whole sentence. There is no published plasma half-life for 5-Amino-1MQ. No peak concentration, no clearance, no volume of distribution, no oral bioavailability figure — not in mice, not in rats, not in a person. That is a fact about the compound rather than a gap in this page, and everything below is what can be computed without those numbers.

Start with the charge, because the rest follows from it. 5-Amino-1MQ is 5-amino-1-methylquinolinium: a quinoline whose ring nitrogen has been methylated. That methyl is a covalent bond, not a captured proton, so the positive charge is permanent — there is no pH anywhere in the body at which this molecule is neutral, which is the opposite of how an ordinary amine drug behaves. The cation is C10H11N2+, 159.21 Da worked out from the formula rather than quoted from a vendor. A permanently charged 159 Da ion is, on paper, precisely the sort of thing that does not cross a lipid membrane, and an orally dosed one should not work at all.

Which makes the single permeability experiment on this scaffold the most load-bearing published fact about it. Neelakantan 2018 put the methylquinolinium series through a parallel artificial membrane assay and a Caco-2 monolayer — the two standard screens for whether a molecule can cross gut epithelium — and reported that the scaffolds carrying a primary amine substitution showed high permeability by both passive and active transport. The 5-amino group is not decoration. It is the permeability fix, and it is the reason an oral cation is a coherent proposition here at all. The same paper dosed diet-induced obese mice systemically and saw body weight, white adipose mass, adipocyte size and plasma total cholesterol fall with food intake unchanged. It reports no exposure, no half-life and no bioavailability. A permeability coefficient across a monolayer of cells is not an oral bioavailability figure and must never be read as one — it measures whether a molecule can cross, not what fraction of a swallowed dose does.

The counter-ion nobody states, and what it costs. A cation cannot be sold on its own; it ships paired with something, and that something is part of what you weigh. Work the arithmetic both ways. As the iodide the formula mass is 286.12, so 200 mg of powder is 111 mg of drug and 89 mg of counter-ion. As the chloride the formula mass is 194.66 and the same 200 mg is 164 mg of drug. Same label, same scoop, a 48% difference in what you actually took. Check the certificate of analysis for the counter-ion before treating a label mass as a drug mass.

The ceiling on exposure, which is computable even though the measurement is missing. Take the 111 mg to 164 mg of cation above: that is 697 to 1,030 micromoles. Spread through roughly 42 L of total body water in a 70 kg adult, with absorption assumed complete and clearance assumed zero, the ceiling is about 17 to 25 µM. Confined to plasma at the instant of dosing it would be 230 to 340 µM. Both are upper bounds by construction — they assume every milligram arrives and none leaves — and the true peak is lower by whatever the gut wall and the liver take first. For an organic cation that is a transporter question rather than a lipophilicity one: OCT1 is the hepatic uptake carrier for this chemical class, so first-pass extraction is something the liver does to the molecule actively, not something a charged molecule passively escapes Koepsell 2020.

How it leaves, and why hours is the right order even without a measurement. Neutral lipophilic drugs are slowed down in the kidney by passive back-diffusion out of the tubule, which requires crossing a membrane uncharged. A permanent cation cannot do that. What it can do is ride the secretory machinery — OCT2 on the blood side of the proximal tubule, the MATE antiporters on the urine side — which is the transport family that handles renal excretion of hydrophilic organic cations Koepsell 2020. Filtered, actively secreted, poorly reabsorbed: that is the profile of something renally cleared quickly. It is an inference from chemistry and it is the best available answer, but it is not a measured renal clearance and should not be quoted as one.

The dosing schedule is the only half-life estimate anyone has published, and nobody published it as one. This is run 2 to 3 times a day for 8 to 16 weeks. Three doses a day is an interval of about 8 hours, and nobody splits a dose three ways for a molecule they think lasts a day. The schedule asserts a half-life of a few hours; the card's “~hours” is that assertion read back out again. It is circular, it originated with protocol writers rather than with a blood draw, and it has never been checked. The catalog's own route comparison is a second implied number worth naming: 50-200 mg swallowed against 25-100 mg by subcutaneous injection is a ratio of about 2x, which prices oral delivery at roughly 50% of what an injection gives. For a permeability-optimized small molecule that is not an absurd guess. It is still a guess.

The read-out that would settle all of this is cheap and has never been run in a human. The enzyme's product is 1-methylnicotinamide. Inhibit NNMT and MNAM should fall, which is target engagement measured rather than inferred from a scale. Neelakantan 2018 watched intracellular MNAM drop in adipocytes; Akerud 2025 tracked plasma MNAM in the rat alongside inhibitor and product and used it to show the mechanism was operating in a living animal. Nobody has drawn plasma MNAM on a person taking 5-Amino-1MQ. One volunteer, a baseline and a series of draws across 8 hours after a single dose, would produce the first exposure curve and the first target-engagement measurement this molecule has ever had in our species.

One complication to state before somebody runs that. MNAM is itself an N-methylated aromatic cation of nearly the same size as the drug, and cations of that description share renal transporters Koepsell 2020. If drug and biomarker compete for the same secretory carriers, plasma MNAM could move for a transport reason rather than an enzymatic one, and a fall would be harder to interpret than it looks. That is a prediction from shared chemistry, not something anybody has tested — and it is testable in a dish, in an afternoon, by anybody with an OCT2-expressing cell line.

What would have to be true, and how you would know it was not

Two predictions fall out of the chemistry, and they point in opposite directions. That is not a hedge — it is what the mechanism actually implies, and a page that only predicted the good one would be advertising.

1. Homocysteine should fall, or at least not rise. NNMT generates S-adenosylhomocysteine, which becomes homocysteine. Inhibit the enzyme and you stop paying that tax. This is the single measurable, falsifiable prediction on the page: draw homocysteine before you start and again at 8–12 weeks, and hold B12, folate and B6 constant across the window, because those move it far harder than this will. If it climbs, the mechanism is not doing what the chemistry says it should.

2. The lipid panel could drift the wrong way, and the liver is why. Hong 2015 reports that the liver carries the highest NNMT expression of any tissue, and that its product methylnicotinamide stabilizes SIRT1 protein — giving MNAM to high-fat-diet mice lowered serum cholesterol, liver cholesterol and liver triglycerides. Read that against the adipose story and the tension is real: the enzyme you are inhibiting for fat loss makes, in the liver, a metabolite that appears to be protective there. Nobody has resolved this in a human, so ApoB and a CMP are the safety half of the draw, not an optional extra.

What nobody has tested yet

Three things that have never been tested and could be, listed because somebody reading this is going to run them on themselves anyway and may as well collect a number while doing it.

Nobody has ever measured homocysteine on an NNMT inhibitor. Not in a trial, because there are none, and not in the self-report record, because nobody thinks to. It costs almost nothing, it is on every standard panel, and it is mechanistically the most direct readout that exists for this compound. A dozen people doing before-and-after draws would produce more information about this molecule in humans than currently exists.

Urinary diacetylspermine is the actual mechanistic biomarker and no human has run it. It is what went up in the mice, it is the direct evidence the futile polyamine cycle is running, and it is a urine test rather than a biopsy. It is not on a standard panel, which is exactly why measuring it would be new information rather than confirmation.

Whether high adipose NNMT predicts who responds. The mouse argument for fat-selectivity is that NNMT is concentrated in white adipose. If that is the mechanism, a lean person has less of the enzyme to inhibit and should respond less — which would explain the consistent theme in the anecdotal record that the effect is subtle. It has never been tested in either direction.

5-Amino-1MQ — its own safety story, not its class's

This is taken by mouth. Nothing on this page about infusion rate, flushing or push speed applies to it, and the NAD+ assay question is not the right question either — the marker here is homocysteine.

The cancer question, which runs the opposite way to most people's instinct. NNMT is upregulated in tumors — esophageal squamous cell carcinoma, gastric cancer, and in the cancer-associated fibroblasts that support tumor growth — and suppressing it raises NAD+ in those cells and slows them. So the directional argument for an NNMT inhibitor in oncology is a positive one, and that is the literature's position rather than a marketing line Sun 2024. What is unknown is the systemic version of that in a person who does not have cancer, over years, which is the timescale people actually use this on.

The real open risk is the methyl economy and the liver. Sparing SAM is the selling point, and SAM is the methyl donor for DNA methylation, catecholamine breakdown and phosphatidylcholine synthesis. Raising it is not obviously neutral, and no one has looked. Combine that with the hepatic MNAM/SIRT1 finding above and the honest summary is that the fat-tissue case is strong in rodents and the whole-body case has never been made in anything.

Sources read for this page

• Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang Y, 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 · PMID 24717514
• Hong S, Moreno-Navarrete JM, Wei X, Kikukawa Y, Tzameli I, Prasad D, Lee Y, Asara JM, Fernández-Real JM, Maratos-Flier E, Pissios P. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nature Medicine 2015;21(8):887–894 · PMID 26168293
• Sun WD, Zhu XJ, Li JJ, Mei YZ, Li WS, Li JH. Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome. Frontiers in Pharmacology 2024;15:1410479 · PMID 38919254
• 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. Biochemical Pharmacology 2018 · PMID 29155147
• Akerud T, De Fusco C, Brandt P, Bergstrom F, Johansson P, Ek M, Borjesson U, Johansson A, Danielsson J, Bauer M, Arnaud B, Castaldo M, Stromstedt M, Rosengren B, Jansen F, Fredlund L. Mechanism and kinetics of turnover inhibitors of nicotinamide N-methyl transferase in vitro and in vivo. Journal of Biological Chemistry 2025 · PMID 40209950
• Koepsell H. Organic Cation Transporters in Health and Disease. Pharmacological Reviews 2020 · PMID 31852803

5-Amino-1MQ — safety, predicted from mechanism

5-Amino-1MQ — interference & stacking

Bloodwork to run alongside 5-Amino-1MQ

Baseline first, then again at 8–12 weeks.

The Metabolic Health & Prediabetes panel covers these in one order — 8 markers, $81.45 with the discount applied.

Check results you already have → · All 103 markers A–Z

5-Amino-1MQ — frequently asked questions

5-Amino-1MQ inside a finished plan

One arm of 3 Protocol Blueprints, free to read in full.

What 5-Amino-1MQ is used for

5-Amino-1MQ appears under 3 goals in the goal router.

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