5-Amino-1MQ: Scientific Profile
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5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule selective inhibitor of NNMT, not a peptide. It restores the intracellular pools of NAD+ and SAM and increases adipocyte beta-oxidation. Reagent for in vitro and preclinical research.
5-Amino-1MQ (5-amino-1-methylquinolinium) is a selective inhibitor of nicotinamide N-methyltransferase (NNMT); it is a small quaternary quinolinium-type molecule, membrane-permeable, not a peptide. NNMT transfers a methyl group from S-adenosyl-L-methionine (SAM) to nicotinamide, generating 1-methylnicotinamide (1-MNA). By inhibiting this reaction, 5-Amino-1MQ blocks SAM-dependent nicotinamide methylation, restores intracellular NAD+ and SAM pools, and increases AMPK signaling and mitochondrial beta-oxidation in adipocytes, reducing adiposity without altering caloric intake in preclinical models. In vitro and preclinical research applications: NAD+ biology, lipid metabolism, adipogenesis and lipolysis, insulin sensitivity, and NNMT-dependent oncology models. Laboratory handling: it is supplied as a crystalline powder; to prepare stock solutions, dissolve in water or DMSO depending on the assay. Storage: keep the solid at -20 C, protected from light and moisture, and the solutions at 2-8 C. Reagent for research (RUO).
Mechanism of action
5-Amino-1MQ is a competitive inhibitor of the active site of NNMT with respect to the substrate nicotinamide, with a reported IC50 of ~1.5 µM. NNMT catalyzes the transfer of a methyl group from SAM to the N1 position of nicotinamide, generating S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide (1-MNA). Inhibition of NNMT produces: (1) accumulation of nicotinamide available for NAD+ resynthesis via the salvage pathway (NAMPT → NMN → NAD+); (2) preservation of SAM pools, an essential substrate for methylation of DNA, histones, and proteins; (3) reduction of 1-MNA, which acts as an inducer of SIRT1 but also as a pro-adipogenic signaling molecule at elevated concentrations. The net effect in white adipocytes is restoration of NAD+-dependent SIRT1/3 activity, an increase in mitochondrial β-oxidation, expression of PGC-1α, and a reduction in adipocyte size. In diet-induced obesity models, 5-Amino-1MQ at a dose of 20 mg/kg/day orally reduces body weight by 7-12% in 11 days without a change in intake. Plasma half-life in mouse: ~2 hours. Predominantly renal elimination. No significant CYP450 metabolism.
Mechanism summary
Selective NNMT inhibitor that blocks the SAM-dependent methylation of nicotinamide to 1-MNA, restores the intracellular pools of NAD+ and SAM and increases AMPK signaling and the beta-oxidation of fatty acids in adipocytes, reducing adiposity without altering caloric intake.
Clinical Studies (7)
- NNMT inhibition reduces fat mass and improves insulin sensitivity (Kannt A, et al. · Diabetes, Obesity and Metabolism · 2024) — Study on NNMT inhibition for the treatment of obesity. PMID 39161060.
- Selective NNMT inhibitors reverse diet-induced obesity in mice (Neelakantan H, Vance V, Wetzel MD, et al. · Biochemical Pharmacology · 2018) — Characterization of 5-Amino-1MQ as a selective, membrane-permeable inhibitor of NNMT in DIO murine models. PMID 29155147.
- NNMT knockdown protects against diet-induced obesity (Kraus D, Yang Q, Kong D, et al. · Nature · 2014) — Genetic validation of the NNMT axis in adipocytes by ASO knockdown, establishing NNMT as a pharmacological target for obesity. PMID 24717514.
- Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice (Dimet-Wiley, et al. · Scientific Reports · 2022) PMID 35013352.
- Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. (Neelakantan H, et al. · Biochem Pharmacol · 2019) PMID 30753815.
- Nicotinamide n-methyltransferase inhibitor synergizes with sodium-glucose cotransporter 2 inhibitor to protect renal tubular epithelium in experimental models of type 2 diabetes mellitus. (Yang Y, et al. · J Diabetes Complications · 2025) PMID 39848127.
- Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice. (Sampson CM, et al. · Sci Rep · 2021) PMID 33707534.
Warnings
5-Amino-1MQ is a research-use-only (RUO) compound; the following warnings and handling considerations apply to its laboratory use:
- Experimental compound without clinical trials in humans
- Chronic safety profile not established
- Potential impact on epigenetics through modulation of SAM
- No long-term carcinogenicity studies
- Unknown interactions with NAD+/NMN/NR supplements
- Exclusive use in controlled research protocols
- Models with known hypersensitivity to 5-Amino-1MQ or excipients
- Pregnant or lactating models (insufficient data in these contexts)
- Models under 18 years of age (limited clinical data)
- Models with severe hepatic or renal insufficiency
- Models with active neoplasia or a recent history of cancer
- Co-administration with potent NNMT inhibitors without supervision
Technical data
- CAS
- 685079-15-6
- Molecular formula
- C10H11N2+
- Molecular weight
- 159.21 Da
- Compound type
- small_molecule
- Storage
- -20°C protected from light and moisture
- Shelf life (lyophilized)
- 24 months at -20°C
- Shelf life (reconstituted)
- 14 days at 4°C in sterile aqueous solution
- Light-sensitive
- Sí
Available for research
5-Amino-1MQ is available as a research reagent (RUO) with HPLC-verified purity and COA per batch:
Frequently asked questions about 5-Amino-1MQ
What is 5-Amino-1MQ?
5-Amino-1MQ (5-amino-1-methylquinolinium) is a selective small-molecule inhibitor of NNMT, not a peptide. It restores intracellular pools of NAD+ and SAM and increases adipocyte beta-oxidation.
What is the mechanism of action of 5-Amino-1MQ?
Selective NNMT inhibitor that blocks the SAM-dependent methylation of nicotinamide to 1-MNA, restores the intracellular pools of NAD+ and SAM and increases AMPK signaling and the beta-oxidation of fatty acids in adipocytes, reducing adiposity without altering caloric intake.
What is 5-Amino-1MQ researched for?
In preclinical research, 5-Amino-1MQ is studied mainly in: research on body composition; models of NAD+ metabolism; studies of adipogenesis and lipolysis. Material exclusively for scientific research.
What are the chemical properties of 5-Amino-1MQ?
Molecular weight 159.21 Da; CAS number 685079-15-6.
How is 5-Amino-1MQ stored?
Storage conditions: -20°C protected from light and moisture; lyophilized stability: 24 months at -20°C; once reconstituted: 14 days at 4°C in sterile aqueous solution; protect from light.
What routes of administration are studied for 5-Amino-1MQ?
In research models the following are described: Oral. Use is exclusively for scientific research.