5-Amino-1MQ

What is 5-Amino-1MQ?

5-Amino-1-methylquinolinium targets a metabolic bottleneck: nicotinamide N-methyltransferase (NNMT), an enzyme that consumes NAD+ precursors by methylating nicotinamide for excretion. By inhibiting NNMT, 5-Amino-1MQ preserves intracellular nicotinamide, allowing its recycling back to NAD+ through the salvage pathway. This mechanism provides an alternative approach to NAD+ augmentation—rather than supplying more precursor, block the pathway that depletes it.

NNMT overexpression correlates with metabolic dysfunction and adiposity in preclinical models, suggesting this enzyme represents a metabolic control point. Research with 5-Amino-1MQ explores NNMT's role in NAD+ homeostasis, methylation reactions, energy metabolism, and the enzyme's potential as a metabolic regulatory target. Note: This is an oral small molecule, not an Liquid Reagent peptide.

Mechanism of Action

5-Amino-1-methylquinolinium functions as a selective competitive inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that catalyzes the methylation of nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as methyl donor, producing 1-methylnicotinamide (1-MNA). By inhibiting NNMT, 5-Amino-1MQ prevents nicotinamide clearance, allowing its recycling back to NAD+ through the salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT). This effectively increases cellular NAD+ pools without supplementing NAD+ precursors—a mechanistically distinct approach to NAD+ augmentation.

NNMT is overexpressed in obesity and metabolic dysfunction, particularly in adipose tissue where it consumes SAM and generates 1-MNA. By inhibiting NNMT, 5-Amino-1MQ preserves SAM for other methylation reactions (histone methylation, DNA methylation) and reduces 1-MNA production. The increase in NAD+ activates sirtuins (particularly SIRT1 and SIRT3), deacetylases that regulate metabolic genes. NNMT inhibition also affects adipocyte gene expression, reducing expression of adipogenic transcription factors PPARγ and C/EBPα. Additionally, the preservation of SAM may enhance epigenetic regulation through DNA and histone methyltransferases. The compound is orally bioavailable as a small molecule, distinguishing it from Liquid Reagent peptide therapeutics.

Key Research Findings

• Inhibits NNMT with IC50 of 3.2 μM in enzymatic assays measuring 1-methylnicotinamide production [Kannt et al., 2015]
• Increases intracellular NAD+ levels by 40-60% in adipocytes after 48 hours treatment at 50 μM [Kraus et al., 2014]
• Reduces body weight by 7% in diet-induced obese mice after 10 weeks without affecting food intake [Kraus et al., 2014]
• Decreases adipocyte size by 35% and white adipose tissue mass by 30% through altered adipocyte differentiation [Brachs et al., 2019]
• Shows 2.1-fold increase in energy expenditure (VO2 consumption) in treated mice vs controls [Kannt et al., 2015]

Reconstitution & Use

Reconstitute with bacteriostatic water for laboratory use. For detailed reconstitution instructions and concentration ratios for your specific research application, see our reconstitution guide.

Storage & Handling

Store at room temperature (15-30°C) in sealed container protected from moisture. This small molecule exhibits excellent stability. For research use, dissolve in appropriate vehicle according to experimental protocol.