5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that sits at the junction of methyl-donor metabolism and NAD+ salvage. Unlike most compounds in our catalogue, 5-Amino-1MQ is not a peptide: it is a methylated quinolinium cation. This article explains what NNMT does, how 5-Amino-1MQ was developed and what the preclinical literature has examined.
For laboratory research use only. Not for human or veterinary use. See our research use only policy.
At a glance: 5-Amino-1MQ identity
- Name: 5-Amino-1MQ
- Synonyms: 5-amino-1-methylquinolinium, 5-amino-1-methylquinolin-1-ium
- Sequence: Not applicable (small molecule, not a peptide)
- Molecular formula: C10H11N2+ (cation)
- Molecular weight: 159.2 g/mol (cation)
- CAS number: Not listed in our catalogue data. As a quaternary cation it is supplied as a salt, and the counter-ion determines the registry entry.
- Form: Lyophilised powder
- Purity: >99% (HPLC)
- Storage: 2-8°C, dark, upright, do not freeze. Keep sealed until use.
What is NNMT?
Nicotinamide N-methyltransferase is a cytosolic enzyme that transfers a methyl group from S-adenosylmethionine (SAM) to nicotinamide, producing 1-methylnicotinamide (MNA) and S-adenosylhomocysteine (SAH). It is expressed most highly in liver, with substantial expression in adipose tissue.
This single reaction touches two important metabolic networks:
- NAD+ metabolism. Nicotinamide is the main precursor recovered by the NAD+ salvage pathway. When NNMT methylates it, that nicotinamide is diverted away from NAD+ resynthesis. Our article on NAD+ vs NMN explains the salvage pathway in detail.
- Methyl-donor balance. Each NNMT reaction consumes SAM, the universal methyl donor used in DNA, histone and protein methylation. NNMT activity therefore has the potential to influence the cellular methylation potential, often expressed as the SAM:SAH ratio.
Interest in NNMT as a research target grew after a 2014 study by Kraus and colleagues in Nature. Using antisense oligonucleotides to reduce NNMT expression in mice, the authors reported changes in adipose tissue SAM and NAD+ levels and in energy expenditure in diet-induced obesity models. This established NNMT as a node linking methylation and NAD+ metabolism in fat tissue in those models.
Development of 5-Amino-1MQ
A research group at the University of Texas Medical Branch, including Harshini Neelakantan and Stanley Watowich, set out to design small-molecule NNMT inhibitors. Their 2017 paper in the Journal of Medicinal Chemistry described structure-activity relationships across a series of quinolinium analogues, which resemble the nicotinamide substrate and the MNA product. Within this series, 1-methylquinolinium compounds bearing small substituents were characterised for NNMT inhibition in enzyme assays.
5-Amino-1MQ emerged as one of the analogues taken forward. A 2018 study by Neelakantan and colleagues in Biochemical Pharmacology reported that it inhibited NNMT, was membrane-permeable in cultured cells, and was associated with increased intracellular NAD+ and SAM and reduced MNA in adipocytes. The same paper investigated the compound in mice with diet-induced obesity and reported changes in body weight, adipose tissue mass and adipocyte size in that model. These are rodent observations and do not establish any effect in humans.
Chemistry and handling considerations
5-Amino-1MQ is a quinoline ring system with a methyl group on the ring nitrogen, which makes that nitrogen quaternary and permanently positively charged, plus an amino group at position 5. Some practical points follow from this structure:
- It is a salt. A permanent cation must be paired with a counter-ion, commonly iodide or chloride depending on synthesis. The formula and molecular weight in our identity data refer to the cation alone (C10H11N2+, 159.2 g/mol), so the weight of the salt will be higher.
- Aromatic amine. Aromatic amines can be sensitive to light and oxidation, which may show as discolouration over time. Storage in the dark is advisable.
- Analytical identity. Mass spectrometry in positive mode should show the cation at m/z of approximately 159. HPLC purity is specified at >99%. For guidance on reading these data, see how to read a peptide certificate of analysis; the principles apply to small molecules too.
Store sealed vials at 2-8°C, in the dark and upright, and do not freeze. Allow vials to reach room temperature before opening. Our article on how to store lyophilised peptides covers general practice for dry research materials.
How 5-Amino-1MQ relates to other metabolic research compounds
5-Amino-1MQ approaches metabolism through enzyme inhibition, which sets it apart from the peptides in this cluster. MOTS-c, the mitochondrial-derived peptide, has been studied as a signalling molecule associated with AMPK and the folate-methionine pathway, which overlaps with NNMT research through shared interest in one-carbon and methyl-donor metabolism. SS-31 is investigated at the level of mitochondrial membrane structure, while AOD 9604 is a growth hormone fragment studied in rodent lipid metabolism. Each tool addresses a different question, and they are not interchangeable.
Limitations of the evidence
The published literature on 5-Amino-1MQ is small and comes mainly from one research group. Studies have been carried out in enzyme assays, cultured cells and mice. Selectivity across the wider family of methyltransferases, long-term behaviour in biological systems and pharmacokinetics are areas where data remain limited. 5-Amino-1MQ is not an approved medicine and has no established use outside laboratory research.
View 5-Amino-1MQ in the catalogue.
Frequently asked questions
What does NNMT stand for?
NNMT stands for nicotinamide N-methyltransferase, an enzyme that methylates nicotinamide using S-adenosylmethionine, producing 1-methylnicotinamide and S-adenosylhomocysteine.
Is 5-Amino-1MQ a peptide?
No. 5-Amino-1MQ is a small molecule, a methylated quinolinium cation with a molecular weight of 159.2 g/mol for the cation. It is supplied alongside peptides but is chemically quite different.
Why is the molecular weight given for the cation only?
5-Amino-1MQ carries a permanent positive charge and is supplied as a salt with a counter-ion. Quoting the cation's formula and weight avoids ambiguity, but the weight of the salt as supplied is higher.
Who developed 5-Amino-1MQ?
It was described by researchers at the University of Texas Medical Branch, including Neelakantan and Watowich, in papers published in 2017 and 2018 as part of a programme on quinolinium NNMT inhibitors.
Is 5-Amino-1MQ approved for human use?
No. It is not an approved medicine. Compound Cave supplies it for laboratory research use only, not for human or veterinary use.
References
- Kraus D, Yang Q, Kong D, et al. (2014). Nature, 508(7495), 258-262. NNMT knockdown in mouse adipose tissue.
- Neelakantan H, Wang HY, Vance V, et al. (2017). Journal of Medicinal Chemistry, 60(12), 5015-5028. Structure-activity relationships of quinolinium NNMT inhibitors.
- Neelakantan H, Vance V, Wetzel MD, et al. (2018). Biochemical Pharmacology, 147, 141-152. 5-Amino-1MQ in adipocytes and diet-induced obese mice.
5-Amino-1MQ gives researchers a defined small-molecule tool for probing NNMT, the enzyme that links nicotinamide disposal to methyl-donor balance.
For laboratory research use only. Not for human or veterinary use. See our research use only policy.