Description

5-Amino-1MQ

Synthetic small-molecule selective inhibitor of nicotinamide N-methyltransferase (NNMT) for in vitro research on cellular NAD+ salvage biology, sirtuin-1 (SIRT1) activation, fatty acid oxidation stimulation, and metabolic flux regulation in adipocytes and myocytes

Overview & Mechanism of Action (In Vitro)

5-Amino-1MQ (5-amino-1-methylquinolin-1-ium iodide/salt) is a synthetic, membrane-permeable small-molecule compound (non-peptidic) engineered as a highly selective inhibitor of the cytosolic enzyme nicotinamide N-methyltransferase (NNMT; IC50≈1.2 μM). NNMT catalyzes the irreversible methylation of nicotinamide (NAM) utilizing S-adenosylmethionine (SAM) as the methyl donor, thereby depleting substrate availability for the NAD+ salvage pathway. In metabolic biology, molecular biogerontology, and cellular bioenergetics, 5-Amino-1MQ serves as the primary reference standard for investigating cellular energy flux modulation:

• Substrate Rescue in the NAD+ Salvage Pathway: Selective inhibition of NNMT prevents the clearance of nicotinamide into 1-methylnicotinamide (1-MNA), significantly increasing NAM availability for the rate-limiting enzyme NAMPT and elevating intracellular NAD+ levels.
• Activation of NAD+-Dependent Enzymes (SIRT1 & PARP): The elevated NAD+/NADH ratio directly stimulates sirtuin-1 (SIRT1) deacetylase activity, initiating downstream deacetylation of PGC-1$alpha$ and driving mitochondrial biogenesis alongside oxidative phosphorylation.
• Cellular Methylation Index Optimization (SAM/SAH Ratio): Attenuating excessive consumption of methyl donors by NNMT increases intracellular SAM bioavailability, modulating DNA and histone epigenetic methylation dynamics in vitro.
• Lipolysis Induction & Lipid Droplet Depletion: Downregulates lipogenic transcription programs in mature adipocytes, elevating cellular oxygen consumption rate (OCR) and accelerating fatty acid β-oxidation without cytotoxic effects.

Technical & Chemical Specifications

• Classification: Research Small Molecule / Selective NNMT Enzyme Inhibitor
• Chemical Name: 5-amino-1-methylquinolin-1-ium (typically supplied as iodide salt / 5-amino-1-methylquinolinium iodide)
• Molecular Formula: C10H11N2+ (cation) / C10H11IN2 (iodide salt)
• Molecular Weight: ≈286.11 g/mol (for iodide salt)
• Form: Sterile white, off-white to yellowish-tan crystalline / lyophilized powder
• Component Identification: Verified via Mass Spectrometry (MS), NMR spectroscopy, and analytical HPLC
• Recommended Dissolution Protocol (Small Molecule Dynamics): The compound exhibits high solubility in DMSO (dimethyl sulfoxide) as well as sterile aqueous buffers depending on the specific salt formulation. For cell culture experiments, prepare a concentrated stock solution in DMSO and dilute into the culture medium to maintain a non-cytotoxic final DMSO concentration (≤0.1%).
• Storage Conditions: Store long-term at -20 °C in a dry, dark environment in a tightly sealed container. Store stock aliquots in DMSO at -80 °C (or -20 °C), protected from repetitive freeze-thaw cycles.

Scientific References & Literature

• Neelakantan, D., et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and enhances myogenesis. Biochemical Pharmacology, 2019.
• Gao, Z., et al. Inhibition of nicotinamide N-methyltransferase improves cellular energy expenditure and insulin signaling in adipocytes. Cell Metabolism, 2015.
• Kraus, D., et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced metabolic dysfunction and regulates NAD+ salvage. Nature, 2014.
• Ruffolo, R., et al. Discovery of membrane-permeable quinoline-based inhibitors of NNMT with potent intracellular target engagement. Journal of Medicinal Chemistry, 2020.

Legal Disclaimer & Terms of Purchase

This product is classified and supplied strictly for laboratory, scientific, and in vitro research purposes only (Research Use Only – RUO). This compound is not a drug, medicine, dietary supplement, cosmetic product, or substance intended for human or veterinary consumption, direct administration, injection, or diagnostic procedures.

By placing an order, the purchaser explicitly confirms that they are at least 18 years of age, possess the requisite professional qualifications and laboratory equipment to safely handle research materials, and are fully conversant with all relevant safety protocols for managing research substances. The seller assumes no liability for any use contrary to these terms.