Research Overview
5-Amino-1MQ, full chemical name 5-amino-1-methylquinolinium iodide, is a small-molecule research compound rather than a peptide. With a molecular weight of 286.13 g/mol and CAS number 62194-86-1, it is supplied here as a 50mg vial of crystalline powder at 99.0% purity verified by HPLC.
The compound is a substrate-mimetic inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that consumes methyl groups from S-adenosylmethionine to convert nicotinamide into 1-methylnicotinamide. Because NNMT activity diverts methyl-group equivalents away from other pathways and is elevated in white adipose tissue in metabolic-disease models, the enzyme has become a target of interest in research investigating adipocyte biology, methyl-donor balance and the salvage pathway of NAD+ biosynthesis.
Researchers use 5-Amino-1MQ as a chemical probe to interrogate these pathways. Its small-molecule structure makes it attractive because it is cell-permeable, stable in standard culture conditions and amenable to combination with peptide research compounds in parallel mechanistic studies. The 50mg vial is supplied by Origin Research and intended exclusively for in-vitro and laboratory research.
Mechanism Studied in Research
5-Amino-1MQ inhibits nicotinamide N-methyltransferase (NNMT), an enzyme that catalyses the transfer of a methyl group from S-adenosylmethionine to nicotinamide, producing 1-methylnicotinamide and S-adenosylhomocysteine.
The compound was identified as a selective small-molecule inhibitor through medicinal-chemistry development by the Vanderbilt group and demonstrated nanomolar potency in enzyme assays. Because NNMT consumes both nicotinamide and methyl-group equivalents, sustained NNMT activity can deplete the cellular pool of nicotinamide available for NAD+ salvage and simultaneously divert SAM-derived methyl groups away from histone, DNA and protein methylation.
In adipose and metabolic research models, inhibition of NNMT has been investigated for its influence on adipogenic transcription factors and lipolytic signalling cascades, with downstream readouts including PPAR-gamma target expression and free-fatty-acid release. 5-Amino-1MQ has been studied for its effect on muscle stem-cell quiescence, regeneration markers and fibre-type composition through preservation of NAD+ and SAM pools.
Research Applications
Adipose-tissue and lipid-metabolism research. 5-Amino-1MQ is used in 3T3-L1 and primary adipocyte cultures to study how NNMT inhibition influences adipogenic differentiation, lipolytic gene expression and lipid-droplet morphology. In rodent diet-induced models, investigators have examined adipose mass, adipocyte size distribution and white-to-brown marker expression following chemical NNMT blockade.
NAD+ salvage and methyl-donor research. By blocking the methylation of nicotinamide, 5-Amino-1MQ is investigated as a tool for preserving NAD+ precursor pools and for shifting the cellular methylation potential. Researchers pair it with nicotinamide riboside and NMN in parallel work monitoring intracellular NAD+, tryptophan metabolites and SAM/SAH ratios as readouts of methyl-donor balance.
Skeletal-muscle stem-cell and regeneration research. NNMT activity is elevated in aged or injured muscle, and 5-Amino-1MQ has been studied as a probe for its influence on satellite-cell activation, MyoD and Pax7 expression, and regenerative response after experimental injury in rodent models.
Methylation-pathway and epigenetic research. Because NNMT competes for SAM with histone and DNA methyltransferases, 5-Amino-1MQ is used in chromatin-focused investigations to test whether enzymatic blockade restores methylation marks or alters DNA methylation patterns.
Reconstitution Reference
5-Amino-1MQ is a crystalline small molecule supplied as the iodide salt and behaves differently from peptide products. It is freely soluble in dimethyl sulfoxide (DMSO) and soluble in water, with DMSO preferred for stock-solution preparation in many cell-culture protocols.
A worked example for the 50mg vial is dissolution in 1.75ml of DMSO, yielding an approximately 100mM stock solution that can be aliquoted into low-binding polypropylene tubes for storage at -20°C. From the 100mM stock, a 10μM working concentration in cell-culture medium gives a typical concentration used in published in-vitro work.
For aqueous stocks, the compound is dissolved in sterile water or PBS at concentrations consistent with reported solubility. Typical in-vitro concentrations fall in the low-micromolar range, and clarity should be verified before use. The stock is filter-sterilised through a 0.22 micrometre filter if it will be added to live-cell cultures.
Storage and Handling
The lyophilised, sealed 50mg vial of 5-Amino-1MQ is stable for at least twenty-four months when stored at -20°C, protected from light and moisture. Small-molecule iodide salts can be light-sensitive, so amber storage or wrapping the vial in foil is recommended even at low temperatures.
DMSO stock solutions are typically stable for several months when stored at -20°C in tightly capped tubes, with care taken to minimise freeze-thaw cycles because DMSO is hygroscopic and absorbs water during repeated thawing. Aqueous stocks should be stored at 2-8°C and used within two to four weeks.
Any solution that develops discolouration or visible precipitate should be discarded. Solid material is kept in a desiccator or with an integrated desiccant pouch to prevent hydrate formation.
References
[2] Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, et al. (2014). Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. PMID 24760551
[3] Neelakantan H, Vance V, Wetzel MD, et al. (2018). Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochemical Pharmacology. PMID 29276697
[4] Pissios P. (2017). Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends in Endocrinology and Metabolism. PMID 28259519
[5] Neelakantan H, Brightwell CR, Graber TG, et al. (2019). Small molecule nicotinamide N-methyltransferase inhibitor activates senescence muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochemical Pharmacology. PMID 31099922