5-Amino-1MQ is a small-molecule NNMT inhibitor central to adipocyte-metabolism and NAD+/SAM research. Full reference: mechanism, target biology, comparison tables and analytical notes.
5-Amino-1MQ (5-amino-1-methylquinolinium; 5A1MQ) is a first-in-class small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), the enzyme that irreversibly methylates nicotinamide using S-adenosyl methionine (SAM) as the methyl donor. It is not itself a peptide, but 5-Amino-1MQ is frequently supplied alongside peptide reference standards in adipocyte-metabolism, NAD+ salvage and SAM-pool research programs across New Zealand.
This reference consolidates the target biology, published in-vitro pharmacology, comparative positioning against peptide metabolism tools and the analytical documentation researchers should expect on a 5-Amino-1MQ certificate of analysis (COA). All content is strictly research-use-only.
Target biology: why NNMT matters in metabolism research
NNMT (EC 2.1.1.1) catalyses the reaction: nicotinamide + SAM → 1-methylnicotinamide (1-MNA) + S-adenosyl-L-homocysteine (SAH). NNMT is expressed at high levels in white adipose tissue and liver in obese-model literature. Because NNMT consumes both nicotinamide (an NAD+ precursor via the salvage pathway) and SAM (the universal methyl donor), pharmacological inhibition preserves NAD+ salvage substrate and cellular methylation capacity simultaneously.
| Metabolic pool | Without NNMT inhibition | With 5-Amino-1MQ (research models) |
|---|---|---|
| Nicotinamide (NAD+ precursor) | Depleted via methylation to 1-MNA | Preserved for NAD+ salvage |
| SAM (methyl donor pool) | Consumed | Preserved for methylation homeostasis |
| 1-Methylnicotinamide (1-MNA) | Elevated | Reduced |
| Cellular NAD+ (adipocyte models) | Baseline | Elevated in published in-vitro work |
Published in-vitro pharmacology
Peer-reviewed literature (Neelakantan et al., Kannt et al., and follow-on adipocyte-model publications) reports 5-Amino-1MQ as a competitive, cell-permeable NNMT inhibitor with an IC50 in the low-micromolar range against recombinant human NNMT. In cultured 3T3-L1 adipocytes and primary murine adipose explants, 5-Amino-1MQ reduces 1-MNA output, elevates intracellular NAD+ and modulates lipogenic gene expression. These are model-system observations only.
Physicochemical & PK properties (research reference)
| Property | Value / Reference |
|---|---|
| Chemical class | Methylquinolinium small molecule |
| Molecular formula | C10H11N2+ (cation) |
| Average mass (cation) | 159.21 Da |
| Typical counterion | Iodide or chloride |
| Aqueous solubility | Freely soluble at physiological pH |
| Cell permeability (in-vitro) | Demonstrated in adipocyte lines |
| Reported IC50 vs hNNMT | Low micromolar (competitive) |
How 5-Amino-1MQ fits alongside peptide research tools
| Compound | Class | Primary research axis |
|---|---|---|
| 5-Amino-1MQ | Small molecule (NNMT inhibitor) | Adipocyte NAD+ / SAM preservation |
| AOD-9604 | Peptide (hGH 177–191 fragment) | Lipolysis / adipocyte research |
| Semaglutide | GLP-1 receptor agonist peptide | Incretin signalling |
| Tirzepatide | GIP/GLP-1 co-agonist peptide | Dual incretin signalling |
| Cagrilintide | Amylin analog peptide | Amylin receptor research |
Documentation checkpoints on a 5-Amino-1MQ COA
- Analytical purity by HPLC (≥98%) with UV method and column reported.
- Identity confirmed by 1H NMR and mass spectrometry consistent with the methylquinolinium cation.
- Counterion identity (iodide vs chloride) explicitly reported — affects mass calculations.
- Residual solvents per ICH Q3C reported for reconstitution planning.
- Batch / lot identifier traceable to the synthesis record and retention samples.
Handling & stability (research reference)
- Store lyophilised powder desiccated at −20 °C, protected from light.
- Reconstituted aqueous stocks are typically stable at 2–8 °C for short-term assay windows; confirm against your lab's stability data.
- Avoid repeated freeze–thaw of reconstituted stocks; aliquot on preparation.
Is 5-Amino-1MQ a peptide?
No. 5-Amino-1MQ is a small-molecule NNMT inhibitor of the methylquinolinium class, not a peptide. It is supplied alongside peptide reference materials because it is central to adipocyte and NAD+ metabolism research programs.
What does NNMT inhibition change at the cellular level?
In published in-vitro adipocyte models, NNMT inhibition preserves both nicotinamide (a direct NAD+ precursor) and SAM (the cellular methyl donor), which is reported to elevate intracellular NAD+ and modulate lipogenic gene programs. These are model observations only.
How does 5-Amino-1MQ compare with peptide research tools like AOD-9604?
5-Amino-1MQ acts intracellularly on the NNMT enzyme, whereas AOD-9604 is a peptide fragment studied against adipocyte lipolysis pathways. They occupy different mechanistic axes and are frequently profiled in parallel in metabolism research.
What analytical characterisation should a 5-Amino-1MQ COA include?
Expect HPLC purity ≥98%, NMR and MS identity confirmation of the methylquinolinium cation, explicit counterion identity (iodide vs chloride), residual solvent testing and batch traceability.
How is 5-Amino-1MQ typically stored for research?
Lyophilised powder is stored desiccated at −20 °C protected from light. Reconstituted aqueous stocks are typically kept at 2–8 °C for short-term assay use; long-term storage should follow your laboratory's validated stability window.
Is 5-Amino-1MQ approved for human use in New Zealand?
No. 5-Amino-1MQ is not an approved therapeutic in New Zealand or elsewhere. It is supplied strictly as a research-use-only reference standard for in-vitro laboratory work.
