5-Amino-1-methylquinolinium Iodide (NNMTi)
5-Amino-1-methylquinolinium Iodide (NNMTi): Properties, Mechanism, and Research Applications
1. Introduction
5-Amino-1-methylquinolinium iodide (commonly referred to as 5-Amino-1MQ or NNMTi) is a cationic quinolinium derivative with an amino group at the 5-position. This compound has gained significant attention in biomedical research as a potent and selective inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme implicated in metabolic disorders, aging, and cancer. Its high water solubility, thermal stability, and ability to form stable complexes make it a valuable tool in chemical analysis, photochemistry, and drug discovery.
2. Chemical Structure and Properties
IUPAC name: Quinolinium, 5-amino-1-methyl-, iodide (1:1)
Molecular formula: C₁₀H₁₁IN₂
Molecular weight: 286.11 g/mol
CAS number: 42464-96-0
MDL number: MFCD22125886
Appearance: Brown to reddish-brown crystalline solid
Purity: ≥98% (typical; research grades ≥99%)
Solubility: Highly soluble in water and polar organic solvents (DMSO, DMF)
SMILES: C[N+]1=CC=CC2=C(C=CC=C21)N.[I-]
Storage: Long-term storage at –20°C recommended
3. Mechanism of Action: NNMT Inhibition
5-Amino-1-methylquinolinium iodide is a substrate site‑targeting, selective inhibitor of nicotinamide N‑methyltransferase (NNMT), with an IC50 of 1.2 µM in biochemical assays. NNMT is an enzyme that catalyzes the N‑methylation of nicotinamide using S‑adenosyl‑L‑methionine (SAM) as a methyl donor. By inhibiting NNMT, this compound modulates NAD⁺ metabolism and sirtuin activity, which are critical pathways in cellular energy homeostasis, aging, and muscle function.
4. Biological Activities and Research Applications
Muscle regeneration and aging: NNMTi promotes myoblast differentiation in C2C12 cells and enhances the fusion and regenerative capacity of senescent muscle stem cells (MuSCs) in aged mice. It activates muscle stem cells and improves skeletal muscle regeneration, making it a promising tool for studying sarcopenia and age‑related muscle decline.
Metabolic disease research: By inhibiting NNMT, the compound aims to modulate metabolic pathways, potentially improving conditions such as metabolic syndrome and obesity. It has been investigated for its role in NAD⁺ pathway repair and sirtuin1 activity regulation.
Oncology: Preclinical studies suggest that NNMTi may reduce tumor growth and enhance the apoptotic effects of anti‑PD‑L1 antibodies in cancer models. NNMT is overexpressed in various cancers, and its inhibition represents a potential therapeutic strategy.
Anti‑aging and longevity: The compound is being explored in the context of cellular senescence, vascular function, and overall healthspan extension.
5. Additional Applications
Chemical synthesis: Used as a pharmaceutical intermediate for the synthesis of heterocyclic compounds, quaternary ammonium derivatives, and active pharmaceutical ingredients (APIs).
Analytical chemistry: Its cationic nature and ability to form stable complexes with transition metals make it useful in colorimetric analysis and as a fluorescent probe.
Photochemistry and materials: Quinolinium derivatives are investigated for applications in organic electronics, fluorescent labels, and biosensors.
6. Safety and Handling
Toxicity: Limited data are available on acute toxicity. As with other quinolinium salts, it may cause irritation upon direct contact with skin and mucous membranes. Standard laboratory safety precautions should be observed.
Regulatory status: Not specifically regulated; however, appropriate waste disposal procedures for iodides and aromatic amines should be followed.
Storage: Store in a cool, dry place, protected from light. Long‑term storage at –20°C is recommended.
7. Conclusion
5-Amino-1-methylquinolinium iodide (CAS 42464-96-0) is a versatile quinolinium derivative with potent and selective NNMT inhibitory activity. Its ability to promote myoblast differentiation, enhance muscle regeneration, and modulate metabolic pathways positions it as a valuable research tool in metabolic disease, aging, oncology, and muscle biology. Beyond biomedical research, its cationic structure and fluorescence properties offer additional applications in chemical analysis and materials science. As research into NNMT inhibition continues to expand, this compound is expected to play an increasingly important role in drug discovery and therapeutic development.