Educational Reference · Research-Use-Only
5-Amino-1MQ: Mechanism, Research, and Regulatory Status
A research-grade overview of 5-Amino-1MQ — what it is, how it works at the molecular level, what published studies have shown, and answers to the questions researchers ask most.
Last reviewed 2026-07-28
What is 5-Amino-1MQ?
5-Amino-1MQ is a cell-permeable small-molecule inhibitor of nicotinamide N-methyltransferase, a cytosolic methyltransferase that transfers a methyl group from S-adenosylmethionine to nicotinamide, yielding 1-methylnicotinamide and S-adenosylhomocysteine. It is not a peptide. Because nicotinamide is the substrate for the NAD+ salvage pathway via NAMPT, high methyltransferase flux diverts nicotinamide away from NAD+ regeneration while simultaneously consuming S-adenosylmethionine, placing the enzyme at the intersection of cellular NAD+ availability and methylation potential.
Expression of the enzyme is markedly elevated in white adipose tissue and liver in obesity, which provided the rationale for pharmacological inhibition. 5-Amino-1MQ is a quinolinium — a permanently charged cation — and membrane permeability was the principal medicinal-chemistry obstacle for this compound class; the reported advance of the methylquinolinium series was achieving intracellular access despite that charge. Neelakantan and colleagues characterized the compound as an analog from their initial inhibitor series with a half-maximal inhibitory concentration of approximately 1 micromolar against the enzyme.
Downstream consequences reported in treated adipocytes and mouse tissue are consistent with restored nicotinamide and NAD+ pools and increased methylation-dependent flux, with associated changes in sirtuin-dependent signaling and polyamine metabolism. A substantial fraction of the inhibitor literature, including several frequently cited metabolic papers, used other compounds in the series or structurally unrelated inhibitors, and those results should not be attributed to 5-Amino-1MQ specifically.
Research highlights
What published peer-reviewed research and preclinical studies have established about 5-Amino-1MQ:
- 015-Amino-1MQ was identified as an analog from an initial NNMT inhibitor series with a half-maximal inhibitory concentration of approximately 1 micromolar against the enzyme (Neelakantan 2018).
- 02In diet-induced obese mice, inhibitor treatment produced weight loss of approximately 5% of body weight, an approximately 35% reduction in epididymal white adipose tissue mass, and greater than 30% decrease in adipocyte size (Neelakantan 2018).
- 03Food intake was unchanged between treated and control groups in that study, indicating the effect was not driven by appetite suppression (Neelakantan 2018).
- 04In a 28-30 day study in diet-induced obese mice, the compound limited weight gain to 0.9 g versus 5.4 g in controls, improved oral glucose tolerance, and reduced microvesicular hepatic steatosis by 73% (Babula 2024).
- 05NEGATIVE DOSE FINDING: in that same study the low-dose arm was not effective, showing weight gain essentially identical to control — the reported metabolic benefits were confined to the high-dose arm (Babula 2024).
- 06ATTRIBUTION CAVEAT: several widely cited NNMT papers do not name 5-Amino-1MQ at all, describing the inhibitor series generally, and one frequently cited metabolic study used a structurally distinct compound entirely. Only two published studies name this compound explicitly.
- 07No human clinical trial of 5-Amino-1MQ or of any NNMT inhibitor is registered on ClinicalTrials.gov, and no human pharmacokinetic, safety, or efficacy data have been published.
Frequently asked questions about 5-Amino-1MQ
What is 5-Amino-1MQ?+
5-Amino-1MQ is a small-molecule research compound — not a peptide — belonging to the methylquinolinium class of nicotinamide N-methyltransferase inhibitors. It is a permanently charged quinolinium cation, usually supplied as the iodide salt, and is used as a chemical probe for studying NNMT function in cellular NAD+ and methylation metabolism. It has never been tested in humans.
What is NNMT and why is it a research target?+
Nicotinamide N-methyltransferase catalyzes the S-adenosylmethionine-dependent methylation of nicotinamide to 1-methylnicotinamide. Because nicotinamide feeds the NAD+ salvage pathway and S-adenosylmethionine is the universal methyl donor, enzyme activity influences both NAD+ availability and cellular methylation potential. Expression is elevated in white adipose tissue and liver in obesity and in various tumor contexts, which is why inhibitors have been developed as research tools.
How strong is the evidence base?+
It is genuinely small and entirely preclinical. A literature search on the compound name returns only a handful of records, and the substantive metabolic work comes from a small number of papers from essentially one research group, using cell-free enzymology, cell culture and mouse models. Only two published studies name the compound explicitly. There are no human data of any kind and no registered clinical trials.
How does it differ from other NNMT inhibitors in the literature?+
The field includes several chemically distinct series — quinolinium compounds like 5-Amino-1MQ, bisubstrate conjugates, and unrelated small molecules. These differ substantially in potency, selectivity, and cell permeability, and results obtained with one are not transferable to another. Papers frequently report results for a generic NNMT inhibitor, so the specific compound identity should be confirmed from the methods section before citing.
Does the salt form matter for preparing solutions?+
Yes, and this is a common source of error. The compound is typically supplied as the iodide salt with a formula weight of 286.11 while the active cation has a mass of 159.21 — a gravimetric preparation based on the salt therefore delivers approximately 55.6% of that mass as the active species. Molar concentrations must be calculated from the salt's formula weight, and published figures should be checked for whether they refer to the salt or the free cation.
How should it be stored and handled?+
Store the solid at -20C, protected from light and moisture. As a charged small molecule it is generally prepared as a DMSO stock for cell-culture work; aliquot stocks and store at -20C or below to avoid repeated freeze-thaw, and confirm the final DMSO concentration is within tolerance for the cell system in use.
References & sources
Every citation below was resolved against its primary source before publication — each PMID against the PubMed record and each DOI through doi.org. Follow any link to read the paper at the publisher rather than taking our summary on trust.
- [1]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. Biochemical Pharmacology. 2018. PMID: 29155147 DOI: 10.1016/j.bcp.2017.11.007
- [2]Babula JJ, Bui D, Stevenson HL, Watowich SJ, Neelakantan H. Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. Diabetes, Obesity and Metabolism. 2024. PMID: 39161060 DOI: 10.1111/dom.15879
- [3]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. Biochemical Pharmacology. 2019. PMID: 30753815 DOI: 10.1016/j.bcp.2019.02.008
- [4]Neelakantan H, Wang HY, Vance V, Hommel JD, McHardy SF, Watowich SJ. Structure-activity relationship for small molecule inhibitors of nicotinamide N-methyltransferase. Journal of Medicinal Chemistry. 2017. PMID: 28548833 DOI: 10.1021/acs.jmedchem.7b00389
- [5]Sampson CM, Dimet AL, Neelakantan H, et al.. Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice. Scientific Reports. 2021. PMID: 33707534 DOI: 10.1038/s41598-021-85051-6
Where this data comes from
- —Citations & trial data: PubMed (NCBI, U.S. National Library of Medicine), Crossref and ClinicalTrials.gov.
- —Chemical identity: PubChem and UniProt. Where sources conflicted, the disputed value is omitted rather than guessed.
- —Regulatory status: U.S. FDA publications and, where applicable, the WADA Prohibited List. Compounding status changes frequently — verify against FDA directly before relying on it.
- —Purity, form and storage are handling and supplier conventions, not literature-derived values. Confirm against the lot-specific certificate of analysis.
Content last reviewed 2026-07-28. Compiled by Veridian Research from the primary literature. This page is an educational reference for laboratory researchers — it is not medical advice, and it describes no human use.
Regulatory status
5-Amino-1MQ is not approved by the FDA, EMA, or any comparable regulatory authority for any indication in humans or animals. It has no marketing authorization, is not a dietary supplement ingredient, and is not an established pharmaceutical. No human clinical trial of 5-Amino-1MQ or of any NNMT inhibitor is registered on ClinicalTrials.gov, and no human pharmacokinetic, safety, tolerability, or efficacy data have been published. The entire published evidence base is preclinical — cell-free enzyme assays, cell culture, and rodent models, drawn largely from a single research group. Supplied strictly as a research chemical for in vitro and non-clinical laboratory investigation — not for human consumption, therapeutic use, veterinary use, or administration to any living subject.
Research-Use-Only Material
Specifications and certificate of analysis
5-Amino-1MQ is stocked as a research reagent. Analytical documentation — identity, purity and the lot-specific certificate of analysis — is published on the product record.
View specifications & COA →