5-Amino-1MQ

What 5-Amino-1MQ is

5-Amino-1MQ is 5-amino-1-methylquinolinium, a small organic cation supplied as a salt. It is not a peptide. It belongs to the catalogue because it acts on the same metabolic territory as the mitochondrial and coenzyme compounds listed alongside it: it is an inhibitor of nicotinamide N-methyltransferase (NNMT), the enzyme that methylates nicotinamide and in doing so consumes S-adenosylmethionine and diverts nicotinamide away from the salvage pathway that regenerates NAD⁺ [1].

The molecule is a quinoline ring with a methyl group on the ring nitrogen, which gives it a permanent positive charge, and an amino group at position 5. The research material is supplied as the chloride salt, a yellow to orange crystalline powder. It was identified by Neelakantan, Watowich and colleagues at the University of Texas Medical Branch in a programme to find membrane-permeable, selective NNMT inhibitors, and it is the compound from that programme most often used as a tool [1, 2].

How the literature describes its mechanism

NNMT transfers a methyl group from S-adenosylmethionine to nicotinamide, producing 1-methylnicotinamide and S-adenosylhomocysteine. The enzyme is expressed mainly in liver and adipose tissue, and its activity has two consequences of interest to metabolic research: it consumes nicotinamide that would otherwise be salvaged into NAD⁺, and it consumes the cell's universal methyl donor. Kraus and colleagues showed in 2014 that knocking down NNMT in liver and adipose tissue protected mice against diet-induced obesity, with increased energy expenditure, and proposed that the enzyme acts as a sink for methyl groups and for NAD⁺ precursors in adipocytes [3]. That paper is the reason NNMT became a drug target.

5-Amino-1MQ was developed as a chemical tool to test the same idea pharmacologically. Neelakantan and colleagues reported a structure–activity series of quinolinium compounds and identified 5-amino-1MQ as a potent, selective NNMT inhibitor with an IC50 in the low micromolar range, high selectivity over related methyltransferases, and, unusually for a permanently charged cation, good cell permeability [1]. Its mechanism of inhibition is competitive with nicotinamide, which it resembles in shape. In cultured adipocytes it raised intracellular NAD⁺ and S-adenosylmethionine and reduced lipogenesis [2].

For an in-vitro programme the relevant readouts are NNMT enzyme activity (typically a coupled fluorescence or LC-MS assay measuring 1-methylnicotinamide formation), intracellular NAD⁺ and SAM levels, lipid accumulation in differentiating 3T3-L1 adipocytes, and markers of adipocyte differentiation. The compound is a tool rather than a drug candidate and has the limitations of one: micromolar potency, a short half-life in animals, and a permanent charge that governs its distribution.

The research record

The published record is preclinical and comes mostly from the group that made the compound. Neelakantan and colleagues reported that 5-amino-1MQ reduced body weight, adipose mass and adipocyte size in diet-induced obese mice over a few weeks, with reduced plasma cholesterol and no observed toxicity at the doses used, and attributed the effect to the NNMT mechanism described above [2]. A later paper from the same group reported that the compound activated senescent muscle stem cells and improved regeneration of aged skeletal muscle in mice after injury [4]. Other groups have since used it as a reference NNMT inhibitor in studies of fatty liver, cancer cell metabolism and adipocyte biology, and improved inhibitors with higher potency have been described. There are no human studies of 5-amino-1MQ.

Regulatory status in the United Kingdom

5-Amino-1MQ has no marketing authorisation and is not a medicine in the UK or anywhere else. It is not controlled under the Misuse of Drugs Act and is not a psychoactive substance within the meaning of the Psychoactive Substances Act. It is supplied as a chemical for in-vitro laboratory use under the Terms of Sale, not for human or veterinary administration. Purchasers must be 18 or over and are responsible for compliance with the laws and institutional rules that apply to them. Our guide to the UK rules on research compounds sets this out in more detail. The compound is not on the WADA Prohibited List by name; its status under the general S4 metabolic-modulator wording has not been tested.

Handling, storage and stability

5-Amino-1MQ is supplied as a crystalline powder in a glass vial. It is a stable organic salt and is handled differently from the peptides in the catalogue.

Sealed vial. Store at room temperature or 2–8 °C, dry and protected from light. The aromatic amine is light-sensitive and darkens on prolonged exposure. Refrigeration is not required for the solid; the compound keeps for years in a sealed, desiccated vial.

Reconstitution. The chloride salt is freely soluble in water, in DMSO and in ethanol. For cell work a stock of 10–100 mM in water or DMSO is usual, diluted into medium at the time of use. There is no lipid chain and no folding, so dissolution is immediate. The molarity calculator gives the mass for a target molar concentration, which is the natural unit for a small molecule.

Solutions. Aqueous and DMSO stocks are stable at −20 °C for months. Protect from light. The compound is a permanently charged cation and will not cross membranes by passive diffusion in the way a neutral small molecule does; it is transported, which is one reason the original papers emphasised its measured cell permeability.

Safety. A small aromatic amine should be handled with gloves and eye protection in a fume hood when weighing the powder. Standard laboratory practice for a research chemical applies; the safety data sheet accompanies the product. The storage and stability guide covers small molecules in a separate section.

What a sound certificate for 5-Amino-1MQ looks like

Every batch we release carries an independent certificate of analysis, transcribed on the product page and in the certificate register. For a small organic molecule the certificate looks different from a peptide's.

Purity by HPLC. Reversed-phase HPLC with UV detection. Unlike most peptides, the quinolinium chromophore absorbs strongly in the ultraviolet and visible range, so purity is reported at 254 nm or at the compound's own absorbance maximum rather than at 214 nm. A good batch shows a single peak at 98% or above.

Identity by LC-MS. The cation appears at m/z 159.1 as the intact quinolinium ion, with no proton added because the charge is already there. The chloride counter-ion is not seen in positive mode. A certificate quoting the salt mass of 194.7 as the observed ion has misunderstood the chemistry.

Identity by NMR. For a small molecule, proton NMR is the definitive identity test and a sound certificate includes it or refers to it. The spectrum should show the N-methyl singlet and the aromatic pattern of a 5-substituted quinolinium.

Water and residual solvent. Karl Fischer water content and residual solvent by GC are standard for a crystalline salt where reported.

What is not applicable. Net peptide content, amino-acid analysis and endotoxin are peptide tests and do not apply; a certificate that reports them for this compound is a template error.

Our guide to reading a certificate of analysis goes through a complete peptide report line by line; the small-molecule items above are the differences.

Related compounds

5-Amino-1MQ sits with the catalogue's NAD⁺-related and mitochondrial compounds. NAD⁺ is the coenzyme whose salvage pathway NNMT competes with. MOTS-c is a mitochondrial-derived peptide studied in the same metabolic models, and SS-31 is a mitochondria-targeted tetrapeptide. None of them shares a mechanism with 5-amino-1MQ, but they are often used together in programmes on cellular energy metabolism.

Frequently asked questions

Is 5-amino-1MQ a peptide? No. It is a small aromatic organic salt, and its handling and certificate follow small-molecule rather than peptide conventions.

Why does the certificate show a mass of 159 rather than 195? The 195 is the chloride salt; the 159 is the quinolinium cation, which is the species the mass spectrometer sees.

Does it need refrigerating? The solid does not, though 2–8 °C does no harm. Keep it dry and out of the light.

Is it the same as 1-methylnicotinamide? No. 1-Methylnicotinamide is the product of the NNMT reaction; 5-amino-1MQ is an inhibitor of the enzyme that makes it.

References

1. 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;60(12):5015–5028. doi:10.1021/acs.jmedchem.7b00389.
2. 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;147:141–152. doi:10.1016/j.bcp.2017.11.007.
3. Kraus D, Yang Q, Kong D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258–262. doi:10.1038/nature13198.
4. 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;163:481–492. doi:10.1016/j.bcp.2019.02.008.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.