5-Amino-1MQ: NNMT Inhibitor Research Guide

5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule, membrane-permeable inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme implicated in obesity, metabolic dysfunction, and aging. Chemical Formula: C₁₀H₁₁N₂⁺ Molecular Weight: 159.21 g/mol CAS Number: 42464-96-0 Classification: Small molecule NNMT inhibitor NNMT catalyzes the methylation of nicotinamide (vitamin B3) to 1-methylnicotinamide (1-MNA), consuming S-adenosylmethionine (SAM) as a methyl donor. High NNMT activity depletes NAD+ and SAM, impairing cellular energy metabolism. 5-Amino-1MQ selectively inhibits NNMT (IC₅₀ = 1.2 μM), preventing nicotinamide degradation and preserving NAD+ availability. By blocking NNMT, 5-Amino-1MQ increases intracellular NAD+ levels: - Mitochondrial energy production (electron transport chain) - Sirtuin activation (longevity pathways, DNA repair) - Cellular metabolism and redox balance - Increases SAM availability for methylation-dependent processes - Reduces lipogenesis and adipocyte size - Improves insulin sensitivity via GLUT4 transporter upregulation | Parameter | Result | |-----------|--------| | Adipocyte size | Decreased >30% | | Adipocyte volume | Decreased >40% | | Total cholesterol | Reduced by 30% | | Lipogenesis | Suppressed 50-70% | | Glucose tolerance | Significantly improved | University of Texas Medical Branch (July 2024) Scientific Reports, 14(1):15554 - Enhanced muscle strength and endurance in aged mice - Rescued aged muscle stem cells (muSCs) - 70% increase in peak torque post-injury - Daily running distance increased 150% Studies in HeLa cervical cancer cells demonstrated: - Concentration-dependent inhibition of cell proliferation - Induction of apoptosis - Decreased oncogenic proteins (phospho-Akt, SIRT1) - Minimal effect on normal HEK-293 cells | Condition | Mechanism | Evidence Level | |-----------|-----------|----------------| | Obesity | Reduces adipocyte size, increases energy expenditure | Validated (DIO mice) | | Type 2 Diabetes | Improves insulin sensitivity | Rodent studies | | Muscle Aging/Sarcopenia | Activates muscle stem cells | Aged mice (2024) | | Athletic Performance | Boosts endurance, reduces recovery | Exercise synergy | | Cancer Metabolism | Inhibits NNMT-driven proliferation | Cancer cell models | - Permeability: High passive membrane diffusion - Selectivity: Does NOT inhibit related SAM-dependent methyltransferases - Safety: No toxicity at doses up to 60 mg/kg/day (mice) - Store lyophilized powder at -20°C - Protect from light and moisture - Reconstitute according to research protocol 1. Neelakantan H et al. (2018) Biochem Pharmacol. 147:141-152. PMC5826726(https://pmc.ncbi.nlm.nih.gov/articles/PMC5826726/) 2. Dimet-Wiley AL et al. (2024) Sci Rep. 14(1):15554. PMID: 38969654(https://pubmed.ncbi.nlm.nih.gov/38969654/) 3. Sun WD et al. (2024) Int Immunopharmacol. 142(Pt B):113208 --- Note: This compound is for research purposes only and is not approved for human