Chemical Name: 5-Amino-1-methylquinolinium CAS Number: 42464-96-0 Enzyme Target: Nicotinamide N-methyltransferase (NNMT) Category: Small-molecule NNMT inhibitor
Research Use Only — Disclaimer
The scientific literature on this page is provided strictly for educational and informational purposes. All Rogue Compounds products are intended for in-vitro laboratory research use only and are not approved by the FDA for human or animal consumption. The studies referenced below are independent third-party peer-reviewed publications. Rogue Compounds makes no claims that any product diagnoses, treats, cures, or prevents any disease or condition. Researchers are responsible for compliance with all applicable local, state, and federal regulations.
What Is 5-Amino-1MQ?
5-Amino-1MQ is a small-molecule research compound investigated as a selective inhibitor of nicotinamide N-methyltransferase (NNMT) — a cytosolic enzyme found primarily in the liver and adipose tissue, with additional expression in skeletal muscle, kidney, and brain. NNMT catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to nicotinamide, converting it into 1-methylnicotinamide (1-MNA). This reaction sits at the intersection of NAD+ metabolism and cellular methylation, making NNMT a subject of growing interest in preclinical metabolic, aging, and muscle biology research.
Mechanism of Action
When NNMT is active it consumes nicotinamide — a key precursor the cell needs to synthesize NAD+ — and converts it into 1-MNA, effectively removing it from the NAD+ salvage pathway. At the same time each NNMT reaction consumes one molecule of SAM, the cell’s primary methyl donor, reducing its availability for histone methylation and other essential biological reactions.
5-Amino-1MQ competitively binds to the NNMT substrate site with an IC50 of approximately 1 micromolar, blocking this conversion. In preclinical cell and animal models this inhibition has been associated with the following downstream changes:
Increased intracellular NAD+ levels, with up to 2-fold elevation reported in adipocytes.
Elevated SAM availability for downstream methylation reactions.
Increased histone H3K4 methylation, shifting gene expression toward a metabolically active profile.
Suppressed lipogenesis in differentiated adipocytes.
Activation of NAD+-dependent sirtuin enzymes including SIRT1 and SIRT3.
Importantly published research has confirmed that 5-Amino-1MQ does not inhibit related SAM-dependent methyltransferases or enzymes in the NAD+ salvage pathway at effective concentrations, indicating a selective mechanism of action.
Published Research
Study 1 — Obesity and Fat Metabolism: Foundational Pharmacology
Authors: Neelakantan et al. Year: 2018 Journal: Journal of Medicinal Chemistry PMID: 29059531 Full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC5826726/
This is the foundational pharmacological study on 5-Amino-1MQ. Researchers at the University of Texas Medical Branch screened a series of quinolinium derivatives for NNMT inhibition and identified 5-Amino-1MQ as the most potent and membrane-permeable candidate.
In cell models: Treatment of differentiated 3T3-L1 adipocytes with 5-Amino-1MQ at 30 micromolar significantly reduced intracellular 1-MNA levels, confirming direct on-target NNMT inhibition. Intracellular NAD+ and SAM levels were confirmed to rise via LC-MS/MS analysis. No cytotoxicity was observed at tested concentrations.
In animal models: Diet-induced obese C57BL/6 mice were treated subcutaneously with 5-Amino-1MQ at 20 mg/kg three times daily for 11 days. Treated mice showed significant reductions in body weight, total fat mass, white adipose tissue mass, adipocyte size, and plasma cholesterol compared to controls. Food intake was not significantly affected and no observable adverse effects were reported.
Study 2 — Muscle Strength and Sarcopenia: Exercise and Aging
Authors: Dimet-Wiley AL, Latham CM, Brightwell CR, Neelakantan H, et al. Year: 2024 Journal: Scientific Reports, Nature Portfolio PMID: 38969654 Full text: https://www.nature.com/articles/s41598-024-66034-9
Published by the University of Texas Medical Branch, this study examined the effects of 5-Amino-1MQ on aged skeletal muscle both alone and in combination with intensive exercise training. Aged mice at 22 months old were treated for 8 weeks and measured across grip strength, running distance, peak torque, fatigue resistance, muscle mass, fiber type, cross-sectional area, intramyocellular lipid content, and full proteome and metabolome analysis.
Sedentary aged mice treated with 5-Amino-1MQ showed approximately 40% greater grip strength than untreated sedentary controls.
Aged mice undergoing exercise training alone showed approximately 20% improvement in grip strength.
Mice receiving both 5-Amino-1MQ and exercise showed approximately 60% improvement in grip strength, suggesting additive and independent mechanisms.
Daily running distances in the combined treatment group increased by approximately 150% and were sustained across the study period, compared to approximately 75% gains in the exercise-only group that tapered off significantly by weeks 7 and 8.
The study authors concluded that NNMT inhibition mimics and amplifies exercise-mediated improvements in aged muscle function and that the two interventions appear to operate through independent molecular pathways.
Study 3 — Adiposity and Gut Microbiome
Authors: Keeble AR et al. Year: 2022 Journal: PubMed PMID: 35013352 Full text: https://pubmed.ncbi.nlm.nih.gov/35013352/
This study examined the combined effect of 5-Amino-1MQ treatment and dietary intervention in diet-induced obese mice. Animals were maintained on a high-fat Western diet for 16 weeks before being randomized to a low-fat diet switch, 5-Amino-1MQ treatment, or a combination of both.
The combination of 5-Amino-1MQ and low-fat diet produced dramatic whole-body fat loss and weight normalization, rapidly bringing treated animals to measures comparable to age-matched lean controls.
Diet switch alone was unable to restore body weight and adiposity to lean control levels within the same timeframe.
5-Amino-1MQ treatment produced a distinct cecal microbiome profile compared to all other groups including the diet-switch-only group, identifying a unique microbial signature associated with NNMT inhibition.
Study 4 — NNMT in Obesity and Type 2 Diabetes: Comprehensive Review
Authors: Liu et al. Year: 2021 Journal: BioMed Research International, Wiley and PMC PMCID: PMC8337113 Full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC8337113/
This peer-reviewed review consolidates the body of preclinical evidence on NNMT’s role in obesity and type 2 diabetes including the research on 5-Amino-1MQ. The review concludes that NNMT inhibition or genetic knockdown significantly increases energy expenditure, reduces body weight and white adipose mass, improves insulin sensitivity, and normalizes glucose tolerance and fasting blood glucose in animal models. The authors validate NNMT as a pharmacological drug target for metabolic disease research and identify 5-Amino-1MQ as a lead small-molecule candidate based on its potency, selectivity, and membrane permeability profile.
Study 5 — Cardiovascular Research: NNMT as Emerging Therapeutic Target
Authors: Jawaria, Zarlashat Y, Philippovich M, Dosa E et al. Year: 2025 Journal: MDPI Biomolecules Full text: https://www.mdpi.com/2218-273X/15/9/1281
This open-access review examines NNMT’s role in cardiovascular disease pathogenesis. The authors identify NNMT-mediated NAD+ depletion as a driver of impaired mitochondrial function, reduced sirtuin activity, elevated homocysteine levels, and activation of pro-inflammatory cascades including TLR4-NF-kB and STAT3-IL-1B signaling. 5-Amino-1MQ is listed as a lead NNMT inhibitor candidate for cardiovascular research. The authors recommend evaluating 5-Amino-1MQ in combination with NAD+ precursors such as NMN in future studies to counterbalance the metabolic consequences of chronic NNMT overactivity.
Current Research Status and Limitations
No human clinical trials investigating 5-Amino-1MQ have been published to date. All evidence currently derives from in vitro cell-based assays and preclinical rodent models. The longest published treatment window in animal studies is approximately 8 weeks. The following remain unestablished in peer-reviewed human research:
Long-term safety profile.
Effects following cessation of treatment.
Oral bioavailability in humans.
Sex-specific differences in response. The 2024 muscle study used aged female mice only.
Appropriate dosing parameters for any application.
Reconstitution Note
5-Amino-1MQ is a small-molecule compound rather than a traditional peptide. Bacteriostatic water is the standard reconstitution solvent used in research settings for this class of compound. Always confirm the recommended solvent against the specific lot datasheet before reconstitution.
In-Use Period and Storage
Before Reconstitution — Lyophilized Powder
Rogue Compounds stores all products refrigerated prior to shipping to maintain compound integrity from production through to delivery. Upon receipt researchers should store vials at 2 to 8 degrees Celsius immediately. Keep vials sealed, dry, and away from direct light until ready for use. Do not freeze. Repeated freeze-thaw cycling has been documented in peer-reviewed pharmaceutical formulation literature to accelerate structural degradation even in dry powder form, potentially compromising molecular integrity and experimental reproducibility.
Why We Refrigerate Instead of Freeze
Freezing and thawing introduces mechanical and osmotic stress at the molecular level. Published pharmaceutical research identifies freeze-thaw cycling as a significant risk factor for loss of structural integrity in peptides and small-molecule compounds. To protect compound quality at every stage of handling and fulfillment, Rogue Compounds maintains refrigerated rather than frozen cold chain storage throughout the entire process.
After Reconstitution — Liquid Solution
Store reconstituted solutions refrigerated at 2 to 8 degrees Celsius immediately after preparation. Protect from light at all stages of storage and handling. Avoid repeated freeze-thaw cycles of reconstituted solutions regardless of the diluent used. Use within the timeframe recommended for the individual compound. Label each aliquot with the compound name, concentration, date of reconstitution, and diluent used. Discard any solution that shows visible particulate matter, discoloration, or signs of contamination.
Note: Storage and in-use recommendations on this page are provided as general laboratory guidance based on standard peptide handling practices documented in peer-reviewed pharmaceutical literature. Researchers should always refer to the individual compound’s published research literature and datasheet for any specific requirements. All products sold by Rogue Compounds are intended strictly for in-vitro laboratory research use only.
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