What it is
5-Amino-1MQ is a cell-permeable synthetic small molecule (not a peptide) — a methylquinolinium analog with an amino substituent at the 5-position and N-methylation at position 1. Molecular formula C10H11N2+, molecular weight 159.21 g/mol, CAS 42464-96-0, PubChem CID 950107. It is typically handled as the iodide salt (conversion factor 1.89 mg salt per 1 mg free cation). The compound was developed as a substrate-site inhibitor of nicotinamide N-methyltransferase (NNMT), a cytosolic enzyme that transfers a methyl group from S-adenosyl methionine to nicotinamide to produce 1-methylnicotinamide (MNA) and S-adenosyl-L-homocysteine. By occupying the NNMT active site, 5-Amino-1MQ preserves the nicotinamide pool available for NAD+ salvage. It was first reported by Neelakantan, Oyer, Richards and colleagues in 2017–2018 as part of a medicinal-chemistry program explicitly aimed at obesity and metabolic disease. It remains an investigational tool compound — not an approved drug — and its human pharmacology is unestablished.
In plain English
5-Amino-1MQ is a lab-made small molecule, not a peptide. It was designed to block an enzyme called NNMT. That enzyme normally chews up a form of vitamin B3 (nicotinamide) that your body uses to make NAD+, an energy molecule. When 5-Amino-1MQ blocks NNMT, more of that vitamin B3 stays available. In theory, that helps keep NAD+ levels from falling. A group of university chemists first reported it in 2017–2018. Their goal was to treat obesity and other metabolic problems. It is still only a research tool, not an approved drug. No one has tested how the human body handles it.
How it works
- 01
NNMT substrate-site inhibition
Neelakantan (2017, Biochem Pharmacol) and Neelakantan (2018, Biochem Pharmacol) characterized 5-Amino-1MQ as a substrate-site NNMT inhibitor. Using recombinant human NNMT with 50 µM SAM and 100 µM nicotinamide, the reported IC50 is ~1.2 µM. Selectivity counter-screens showed no inhibition of related SAM-dependent methyltransferases DNMT1 and PRMT3, nor of the NAD+ salvage enzymes NAMPT or SIRT1, at concentrations up to 600 µM. This isolates the downstream metabolic effects to NNMT blockade rather than confounding off-target effects.
In plain English
It blocks the NNMT enzyme by sitting in its active slot
Think of the NNMT enzyme like a keyhole. 5-Amino-1MQ acts like a blank key that fills the slot so nothing else can fit. In lab tests, it blocked NNMT at low doses. It left four similar-looking enzymes alone, even at doses 500 times higher. That means the effects it produces are probably from blocking NNMT, not something else by accident.
- 02
Preservation of the NAD+ salvage pool
NNMT is the only enzyme that catabolizes nicotinamide to MNA; by inhibiting NNMT, 5-Amino-1MQ spares nicotinamide for NAMPT-catalyzed reconversion to nicotinamide mononucleotide and onward to NAD+. In 3T3-L1 adipocytes Neelakantan (2018) measured an MNA-suppression EC50 of ~2.3 µM with a concurrent rise in intracellular NAD+. The magnitude of NAD+ elevation in tissues beyond adipose has been less consistently quantified, and no human tissue NAD+ pharmacodynamic data has been published.
In plain English
It helps keep NAD+ (an energy molecule) from running out
Your cells recycle a form of vitamin B3 (nicotinamide) back into NAD+, an energy molecule. NNMT is the only enzyme that breaks nicotinamide down and throws it away. Block NNMT, and more raw material stays around for recycling. In fat cells in a dish, NAD+ did go up. Whether this actually happens in human tissue has never been measured.
- 03
Adipocyte lipogenesis suppression
In differentiated 3T3-L1 adipocytes, 5-Amino-1MQ suppresses de novo lipogenesis with an EC50 near 30 µM (Neelakantan 2018) without measurable cytotoxicity at 10 µM for 24 h. The proposed chain is NNMT inhibition → nicotinamide and NAD+ preservation → restored NAD+-dependent sirtuin activity → reduced lipogenic gene expression and improved mitochondrial fuel oxidation. The in-vivo correlate is smaller adipocytes and reduced white-adipose mass in diet-induced-obese mice at 20 mg/kg subcutaneous dosing.
In plain English
It slows down fat-making inside fat cells
In fat cells in a dish, 5-Amino-1MQ slowed down how much new fat those cells made. The likely chain: block NNMT, keep more NAD+ around, then turn on cell machinery that burns fuel instead of storing it. In obese mice, this showed up as smaller fat cells and less white fat overall.
- 04
Skeletal-muscle regenerative signaling (preclinical)
Watowich (2022, Biogerontology) reported that in aged mice, 5-Amino-1MQ treatment after tibialis-anterior muscle injury increased satellite-cell (MuSC) proliferation, enlarged myofiber cross-sectional area, and raised post-injury peak torque by ~70% versus vehicle. Sedentary aged mice showed ~25% grip-strength gain; animals that also ran wheels showed ~60%. The mechanistic narrative is NAD+/SIRT1-mediated restoration of muscle-stem-cell metabolic fitness. This is a single-lab finding in mice and has not been independently reproduced as of April 2026.
In plain English
It may help aged muscle grow back stronger — in mice
In a 2022 study, old mice got a leg-muscle injury. The ones given 5-Amino-1MQ grew back thicker muscle fibers. They also had about 70% more power than mice on placebo. Old mice that didn't exercise gained about 25% grip strength. Those that ran on wheels gained about 60%. The idea is that raising NAD+ wakes up muscle stem cells. One big warning: only one lab has ever reported this, and only in mice. No one has repeated it yet.
- 05
Downstream metabolic and microbiome effects
Dimet-Wiley (2021, Scientific Reports) showed that combining 5-Amino-1MQ with a low-fat-diet switch in DIO mice accelerated weight and adiposity normalization and shifted gut microbiome composition. Hong (2021, BioMed Res Int) reviewed a broader set of rodent data suggesting that NNMT inhibition raises GLUT4 expression, improves insulin sensitivity, and may drive formation of PAHSAs — insulin-sensitizing lipids. These downstream effects are plausible but the specific contribution of 5-Amino-1MQ (as opposed to NNMT inhibition more generally, including by genetic knockdown) is not fully disentangled.
In plain English
It may shift gut bacteria and insulin response
A 2021 study put obese mice on a low-fat diet. The ones that also got 5-Amino-1MQ lost weight faster, and their gut bacteria shifted. Other rodent work hints that blocking NNMT may help muscles pull sugar out of the blood. It may also make the body more sensitive to insulin. All of this is plausible. But it hasn't been cleanly separated from what happens when NNMT is blocked in other ways (like genetically deleting it).
- 06
What is NOT known about the mechanism
Human pharmacokinetics of 5-Amino-1MQ have not been published. Rat PK shows substantial plasma exposure after IV and oral dosing, but human absorption, distribution, metabolism, elimination, plasma half-life, and tissue NAD+ response are all unreported. The compound carries a permanent positive charge on the quinolinium nitrogen; cellular uptake and blood–brain-barrier penetration in humans have not been demonstrated. Long-term consequences of sustained NNMT inhibition — in particular on one-carbon metabolism, SAM/SAH balance, and epigenetic methylation — have not been studied past short rodent exposures.
In plain English
What we still don't know
No one has published how the human body handles 5-Amino-1MQ. We don't know how much gets absorbed, how long it stays, how fast it clears, or whether it actually raises NAD+ in human tissue. Rat data exists, but rats aren't people. The molecule also carries a permanent electrical charge. That can make it hard for cells to absorb and hard for it to reach the brain. No one has tested that in humans. And shutting down NNMT also touches the cell machinery that manages DNA methylation and other key chemistry. The long-term effects of that have never been studied beyond a few weeks in rodents.